Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Review

Free Access

The True Story and Advantages of RNA Phage Capsids as Nanotools

Pumpens P.a · Renhofa R.a · Dishlers A.a · Kozlovska T.a · Ose V.a · Pushko P.c · Tars K.a, b · Grens E.a · Bachmann M.F.d, e

Author affiliations

aLatvian Biomedical Research and Study Centre, and bFaculty of Biology, Department of Molecular Biology, University of Latvia, Riga, Latvia; cMedigen Inc., Frederick, Md., USA; dJenner Institute, University of Oxford, Oxford, UK; eUniversity Institute of Immunology, University of Bern, Inselspital, Bern, Switzerland

Corresponding Author

Paul Pumpens

Baznicas 27/29-22

LV-1010 Riga (Latvia)

E-Mail paul@biomed.lu.lv

Related Articles for ""

Intervirology 2016;59:74-110

Abstract

RNA phages are often used as prototypes for modern recombinant virus-like particle (VLP) technologies. Icosahedral RNA phage VLPs can be formed from coat proteins (CPs) and are efficiently produced in bacteria and yeast. Both genetic fusion and chemical coupling have been successfully used for the production of numerous chimeras based on RNA phage VLPs. In this review, we describe advances in RNA phage VLP technology along with the history of the Leviviridae family, including its taxonomical organization, genomic structure, and important role in the development of molecular biology. Comparative 3D structures of different RNA phage VLPs are used to explain the level of VLP tolerance to foreign elements displayed on VLP surfaces. We also summarize data that demonstrate the ability of CPs to tolerate different organic (peptides, oligonucleotides, and carbohydrates) and inorganic (metal ions) compounds either chemically coupled or noncovalently added to the outer and/or inner surfaces of VLPs. Finally, we present lists of nanotechnological RNA phage VLP applications, such as experimental vaccines constructed by genetic fusion and chemical coupling methodologies, nanocontainers for targeted drug delivery, and bioimaging tools.

© 2016 S. Karger AG, Basel


Family of RNA Phages

Taxonomy

Pili-specific RNA phages, currently the most promising virus-like particle (VLP) carriers, are nonenveloped, spherical viruses with T = 3 icosahedral symmetry and diameters ranging from approximately 28 to 30 nm. RNA phage particles are composed of 178 chemically identical coat protein (CP) molecules, or 89 CP dimers, and one copy of maturation, or A, protein, which replaces a single CP dimer. The phage's monopartite, positive-sense, single-stranded (plus-ssRNA) genome is approximately 4 kb in size and serves as messenger RNA for the synthesis of the capsid-forming CP as well as three other viral proteins: the maturation, replicase, and lysis proteins (fig. 1).

Fig. 1

Genomic structure of RNA phages that have been used in viral nanotechnology applications. a Locations of the CP genes (colored in dark pink) within the genomes of RNA phages. The genomes are shown to scale and are in alphabetical order. AP and A2 are maturation proteins. RP = Replicase; L = lysis protein. The Qβ genome does not encode L protein. The A1 extension of the Qβ CP is indicated in light pink. The numbering used for CP aa residues is indicated for each species. The data are compiled from the NCBI taxonomy browser for the Leviviridae family [19]. The experimentally determined lengths of phage CPs are always one aa residue shorter than the actual proteins because the N-terminal methionine is cleaved off in infected E. coli cells. This explains the discrepancies in CP numbering in different published works. b The phenogram of the CP aa sequences obtained by Clustal V alignment in the MegAlign program from DNASTAR Lasergene.

http://www.karger.com/WebMaterial/ShowPic/525639

The first Escherichia coli-infecting RNA phages that played an important role in VLP technology were identified in the early 1960s and included the f2 [1], MS2 [2], R17 [3], fr [4], M12 [5], and Qβ [6] phages. The early history and basic properties of RNA phages were reported in detail in two books [7,8] and in one original review [9].

Later, other RNA phages that became more common as VLP carriers were described, including the E. coli phages SP, FI [10] and GA [11], the Caulobacter crescentus phage φCB5 [12], the Pseudomonas aeruginosa phage PP7 [13], the broad host range, P-pili-specific phage PRR1 [14], and the Acinetobacter phage AP205 [15,][16].

According to the most current ICTV taxonomy release [17], RNA phages are members of the family Leviviridae. This family has not been assigned to any higher viral order and comprises two genera: Levivirus, which includes the species BZ13 (first mentioned in Inokuchi et al. [18]) and MS2, and Allolevivirus, which includes the species FI and Qβ. Other common RNA phages were mentioned in earlier ICTV taxonomy releases until 1998.

According to current NCBI Taxonomy browser information [19], the Levivirus genus consists of the BZ13 and MS2 species. The BZ13 species includes the phages GA and JP34, among others, as subspecies, while the MS2 species includes the phages f2, fr, M12, and R17, among others. The Levivirus genus also includes some unclassified members such as the Acinetobacter phage AP205 and the Pseudomonas phage PP7.

Based on the NCBI Taxonomy classification of the Allolevivirus genus, the FI and Qβ species include FI group subspecies (including phages SP, TW19, and TW28, among others) and Qβ group subspecies (including phages MX1 and ST, among others). Some species, including the Caulobacter phage φCB5 and P-pili-specific phages, predominantly the Pseudomonas phage PRR1, remain in the NCBI classification as unclassified Leviviridae members.

Sero- and Genogroups

Generally, the current classification is based on serological typing [20] and has divided RNA phages into four serogroups, namely, serogroups I to IV [for a detailed discussion, see [21]]. This classification scheme has been confirmed by studies of the template specificity of RNA phage replicases [22], genetic analysis [23,24], and physiochemical data, e.g. by resistance to high hydrostatic pressure [25]. The RNA phages MS2, GA, Qβ, and SP are typically recognized as reference strains for the sero- and genogroups I, II, III, and IV, respectively. Therefore, group I and II members belong to the Levivirus genus, while serogroup III and IV members belong to the Allolevivirus genus. Ecological and wastewater studies have revealed that RNA phages from groups II and III are associated with human waste, whereas group I and IV members are predominantly associated with animal waste [21]. However, this distribution is not absolute and requires further refinement [26,27].

The genomic structures of the Levivirus and Allolevivirus genera members demonstrate some differences (fig. 1). In addition to the standard maturation protein, CP, and replicase subunit, the Allolevivirus genome encodes a C-terminally extended CP known as the minor A1 protein, which appears as a result of ribosomal read-through of a leaky opal termination codon of the CP gene [28] and is essential for the formation of viable Qβ particles in vivo [29,30,31]. The A1 protein is incorporated in 3-10 copies per virion, or in 12 copies in accordance with a recent study [32], it is required for infection, but its precise function is not known [for more references, see [8,29,30,31,32,33]]. A recent electron microscopy visualization of foreign epitopes carried by A1 protein within infectious Qβ particles showed that the A1 protein molecules are occupying corners of the Qβ icosahedron [32]. The lysis protein forms pores in the cellular membrane, leading to activation of autolysins and, eventually, cell lysis [34].

Drawbacks of Classification

The current NCBI classification comprising two genera as well as four serogroups are adequate in the case of coliphages; however, attempts to assign phages from other hosts to Levivirus, Allolevivirus, or ‘unclassified' members have been rather artificial and lack solid rationale aside from historical considerations. In our opinion, a new classification system based solely on sequence similarities should be employed. For example, Levivirus and Allolevivirus genera could be left only for coliphages, and new genera could be introduced based on sequence similarities among conserved replicase protein sequences.

Unique Scientific Role

RNA phages were the first classic models used in early molecular biology and are considered ‘instrumental in the making of molecular biology' [35]. They provided the scientific community with purified RNA and markedly contributed to the decryption of the genetic code, the understanding of RNA translation and replication mechanisms, and the elucidation of virus-host interactions and the self-regulation of biological systems [for details and references, see [7,8,9,35]]. The RNA phage MS2 was the first organism with a fully sequenced genome [36]. The capsids of the RNA phages R17 and f2 were among the first observed virions with resolved icosahedral symmetry [37], after the classical work by Caspar and Klug [38] on the structural analysis of plant viruses. RNA phages have also presented substantial background for studies on phylogeny and genome evolution [33].

Furthermore, RNA phages paved the way for antisense-based gene therapy via the generation of the so-called ‘mRNA-interfering complementary RNA (micRNA) immune system' for the prevention of phage SP proliferation [39,40].

RNA phages, especially the phage MS2, have also markedly contributed to ecological and disinfection studies via their use in the development of numerous physical and chemical methods for genome inactivation, from early attempts [41] to recent systematic studies [42]. The RNA phages MS2, GA, Qβ, FI, SP, and PP7 are still efficiently used as surrogate models for the control of viral contamination in food production and storage, in industrial and clinical applications, and on health care personnel [for two recent examples, see [43,44]], in addition to serving as viral and microbial source tracking materials in wastewater [for references and discussion, see [45]]. It is broadly accepted that RNA phages are fully adequate surrogates for human enteroviruses in studies of virus contamination [46,47]. RNA phages are also often used as internal controls of extraction/amplification efficiency in modern RT-PCR kits for the surveillance of emerging pathogens, including the Ebola virus [48].

CP as a Repressor

RNA phages were the first examples of an ‘operon' mechanism of gene regulation by ‘self' proteins [49]. This mechanism can be described as a full-cycle regulated biological system, where gene regulation is performed by two phage proteins: CP and replicase [50,51]. The CPs of most RNA phages have been shown to repress translation of the replicase gene by binding to an RNA hairpin as an operator at the start site of the replicase gene [7,8,9]. The ability of RNA phage CP to recognize the corresponding operator stem-loop led to the development of an efficient methodology based on the tethering of CP to CP-operator-tagged RNAs. Using this technique, mRNAs that are tagged with the operator sequence are highly specifically recognized by CP, which can be fused to fluorescent or other functional probes. This CP-operator tethering methodology enables imaging of the processing, export, localization, translation, and degradation of operator-tagged mRNA in living cells (see the review by Lampasona and Czaplinski [52] and a recent protocol from Bensidoun et al. [53] as an example). Furthermore, the tethering technique allows affinity purification of the desired RNA-protein complexes [54]. The tethering methodology mostly exploits the CP-operator composition from phage MS2, although PP7-based methodology, including the use of simultaneous MS2 and PP7 two-color labeling [55], has been recently described. A phage R17-based technique was also used in the early development of the tethering approach [56]. It is noteworthy that the tethering technique has recently been applied to further develop the highly productive CRISPR-Cas9 technology [57].

Expression and Structural Investigations

Expression of CP Genes

The expression of RNA phage CP genes in E. coli led to the high-level production of correctly self-assembled icosahedral capsids that were morphologically and immunologically indistinguishable from virions in the case of MS2 [58,59] and fr [60] of group I, JP34, an intermediate between groups I and II [61], GA of group II [62], Qβ of group III [63], SP of group IV [64], the unclassified Levivirus members PP7 [65,66] and AP205 [67,68], and the unclassified Leviviridae phages PRR1 [69] and φCB5 [70]. It is noteworthy that not only E. coli cells but also the E. coli-based cell-free translation system can be used for efficient in vitro production of MS2 VLPs [71,72].

Coinfection with two phages led to the production of mixed particles only in the case of the closely related phages MS2 and fr from the serogroup I and not in the case of the more distantly related phages fr and GA; however, the reassembly of recombinant fr and GA CP dimers in vitro allowed the generation of the mixed particles in both spherical and rod-like configurations [73].

Highly efficient production of VLPs was also achieved in the yeast species Saccharomyces cerevisiae and Pichia pastoris for phages MS2 [74], Qβ [75], GA [76], fr, AP205, PP7, and φCB5 [77]. Attempts to prepare RNA phage SP VLPs in S. cerevisiae and P. pastoris were unsuccessful [77].

3D Structures of Phage Capsids

As mentioned above, the RNA phages R17 and f2 played a unique role in revealing the virion's icosahedral symmetry [37]. The place of RNA phages in the global history of viral architecture was presented in a recent review [78]. Early electron microscopy studies demonstrated clear paracrystalline arrays of virions in E. coli cells infected with the RNA phages f2 [79], µ2 [80], and R17 [81]. Similar paracrystalline structures were later found in E. coli cells expressing the CP gene and producing VLPs; for example, see the electron micrograph of a slice of a cell filled with phage Qβ VLPs in Pumpens and Grens [82].

Fine 3D structures of the most typical RNA phage representatives have been resolved by X-ray crystallography (fig. 2) and were found to be very similar, despite the marked diversity in the primary structures of their CPs (fig. 1). The first 3D structure resolved was for MS2 virions. At the time, this structure showed no similarity to any other known viruses or proteins of any origin. The MS2 virion structure was first determined at a resolution of 3.3 Å [83,84,85] and then refined to a resolution of 2.8 Å [86]. Next, the crystal structure of an MS2 capsid with amino acid (aa) exchanges in the FG loop was resolved [87]. Historically, the first phage MS2 crystals and preliminary X-ray examination data were obtained in Walter Fiers' lab in 1979 [88].

Fig. 2

Crystal structures of RNA phages that have been used as VLP carriers. The structures are presented in alphabetical order with their protein data bank IDs shown in parentheses and the outer diameters indicated for each species. The AB loops are exposed on the full-capsid surfaces. Also shown are the corresponding trimeric asymmetric units with the indicated N- and C-termini. The outer surface is oriented towards the reader. The AB loops are indicated by arrows. The Qβ AB loops are distinguished by Lys14 residues, which are indicated by the shaded areas. The CP chains A, B and C are indicated in red, green, and blue, respectively. The structural data are compiled from the VIPERdb (http://viperdb.scripps.edu) database [389] and were visualized using Chimera software [390].

http://www.karger.com/WebMaterial/ShowPic/525638

According to the 3D structure of MS2, the 180 CP subunits of the virion are arranged in dimers as initial building blocks and form a lattice with a T = 3 triangulation number (fig. 2). The CP subunit consists of a five-stranded β-sheet facing the inside of the particle and a hairpin and two α-helices on the outside.

The structure of a recombinant capsid of the RNA phage fr was determined by X-ray crystallography at a resolution of 3.5 Å and was shown to be identical to the protein shell of the native virus [89,90]. This was followed by determination of the structure of the GA phage, which showed some structural differences compared to MS2 and fr phage/VLPs, especially in the N- and C-terminal regions [91]. The structures of virions and recombinant capsids of the Qβ phage were resolved at a resolution of 3.5 Å [92,93]. These structures differed from previously determined RNA phage structures by the presence of stabilizing disulfide bonds on each side of the flexible FG loop, which covalently links CP dimers. A comparison with the structure of the related phage MS2 shows that although the fold of the Qβ CP is very similar, the details of the protein-protein interactions are completely different [93].

The crystal structure of the P. aeruginosa phage PP7 was resolved at a resolution of 3.7 Å [94,95]. As in the case of the MS2 and Qβ CPs, the RNA recognition site on the PP7 CP was determined [96]. Recently, a detailed biophysical study of PP7 virions, including the effects of pH and salt concentration on the charge transition from net-positive to net-negative, was undertaken [97]. The crystal structure of another Pseudomonas phage, PRR1, was resolved at a resolution of 3.5 Å and exhibited a binding site for a calcium ion close to the quasi-3-fold axis [69].

The crystal structure of a very distant RNA phage, the Caulobacter phage φCB5, was resolved at 3.6 Å, and the structure of a φCB5 VLP was resolved at 2.9 Å [70]. The structures appeared to be nearly identical, with some differences in the average density of RNA. Unlike in other phages, φCB5 capsids are significantly stabilized by calcium ions, similarly to some plant viruses [98]. Disassembly of these capsids occurs when the calcium ions are chelated with EDTA and/or there is a reduction in the surrounding salt concentration. Another unique feature of φCB5 is the involvement of RNA bases in the stabilization of its interdimer contacts [70].

Recently, the crystal structure of a phage AP205 dimer was solved at a resolution of 1.7 Å and then fitted into a 6.6-Å resolution cryo-EM map [99]. The structure of the AP205 CP dimer can be regarded as a circular permutant relative to the structures of MS2 and other family members (fig. 3). This feature is made possible by the fact that the N-terminus of one monomer in the dimer is in close proximity to the C-terminus of the other monomer. Compared to MS2 and other phages with known structures, the AP205 CP is missing one beta strand in its N-terminus, but it has an extra beta strand in its C-terminus. However, when considered from a 3D perspective, the position of the beta strand is essentially the same in both cases. As a consequence, AP205 has N- and C-termini in the same locations as those occupied by surface-exposed AB loops in other phage capsids. It is notable that the N- and C-termini in other phages are not well exposed on the surface and are clustered around the quasi-3-fold axes. This explains the previous observations that, in contrast to other phages, the AP205 CP can tolerate long additions at its N- and C-termini without compromising capsid assembly [67].

Fig. 3

Differences in CP structures between the AP205 and MS2 phages. The overall folds of the CP dimers (top) are similar for both phages. The CP monomers are shown in rainbow coloring, from the blue N-terminus to the red C-terminus. From the more schematic picture of secondary structure elements (middle), it is obvious that AP205 has N- and C-termini that are located in roughly the same place as the AB loops from MS2. As a result, the N- and C-termini in AP205 are well exposed on the capsid surface (blue and red, respectively), similarly to the AB loops (black) in MS2.

http://www.karger.com/WebMaterial/ShowPic/525637

In addition to the structures of self-assembled RNA phage capsids, the crystal structures of unassembled mutant CP dimers of MS2 [100] and GA [62] have also been resolved. These structures showed only minor differences in comparison to their self-assembled counterparts. Surprisingly, the MS2 CP sustained a genetic fusion, resulting in a duplicated CP that folded normally and functioned as a translational repressor due to its physical proximity to the N- and C-termini of the CP [101].

Furthermore, the crystal structure of an icosahedral MS2 capsid that was assembled from covalently joined dimers, or so-called single-chain dimers, was resolved at 4.7 Å [102]. The structure resembled the wild-type (wt) virion except for the intersubunit linker regions, but a fraction of the capsids was unstable in phosphate buffer because of assembly defects [102]. Moreover, the organization of MS2 single-chain dimers into crystals may have resulted in an arrangement of subunits that corresponds to T = 3 octahedral particles [103]. In this case, the arrangement of dimers is somewhat similar to that in normal T = 3 icosahedral particles, except that four FG loops interact near the 4-fold axis of symmetry on an octahedron rather than five FG loops interacting near the 5-fold axis of symmetry on an icosahedron. However, when MS2 CP dimers are not crystallized in the F cubic crystal form, they are assembled into T = 3 icosahedral capsids that are indistinguishable from the wt particles [103].

Structural Basis of RNA Recognition

X-ray crystallography led to a breakthrough in understanding the protein-RNA interactions that occur during translational repression and genome encapsidation. This breakthrough was particularly apparent after the first crystal structure of a complex of recombinant MS2 capsids with the 19-nucleotide RNA operator was resolved at 2.7 Å [104,105,106]. The residues responsible for the protein-RNA interactions were localized by analysis of aa exchanges at positions 45 and 59 [107,108,109]. Furthermore, numerous other mutations responsible for altering the specificity [110] and efficiency [111] of translational operator complexes were identified. The crystal structures of MS2 VLPs complexed with RNA aptamers, which differ in secondary structure from wt RNA [112,113,114] or involve the presence of 2′-deoxy-2-aminopurine at the critical -10 position [115], have also been resolved.

Structures of CPs in complex with operator RNA fragments have also been solved for PRR1 [116], PP7 [117], and Qβ [118]. The CP dimers formed by the RNA phages studied to date all recognize a stem-loop sequence around the replicase start codon. This CP-RNA interaction serves as a mechanism for translational repression and self-genome recognition during virion assembly. Although the overall binding mode of the stem-loop to CP is similar in all the studied cases, the details are surprisingly different among different viruses. A number of nucleotides form sequence-specific and sequence-unspecific interactions with CPs. For CP recognition, the most important nucleotides are two adenosines, one located in the loop region and another in a stem bulge. In MS2, PP7 and Qβ, these adenosines form quite different interactions with the CP dimer (fig. 4). It should be noted that we have failed to identify analogous CP-RNA interactions in the more distantly related phages AP205 and φCB5 [K. Tars, unpubl. observations], suggesting that mechanisms of genome recognition and translational repression may differ significantly among distant Leviviridae family members.

Fig. 4

Different binding modes of operator stem-loop sequences to CP dimers from MS2, Qβ, and PP7. For the operator stem-loop sequences, adenosine, which is required for the binding of loop nucleotides, is shown in red, while bulged adenosine is shown in blue. The replicase gene initiation codon is boxed.

http://www.karger.com/WebMaterial/ShowPic/525636

Electron cryomicroscopy studies have shown that, in addition to the operator, many other RNA sequences in the MS2 genome are able to bind to the CP dimer [119]. Such studies have allowed 3D visualization of icosahedrally averaged genomic MS2 RNA at a resolution of 9 Å [120]. Recently, direct evidence for packaging signal-mediated assembly of the MS2 phage was presented based on cross-linking studies of peptides and oligonucleotides at the interfaces between the capsid proteins and the genomic RNA of this phage [121,122]. Remarkably, the same CP-RNA and maturation protein-RNA interfaces were identified in every viral particle.

The A Protein

Particles of RNA phages contain a single copy of a maturation protein, also known as the A protein, which binds to genomic RNA and is absolutely necessary for the infectivity of phages by attachment to bacterial pili. Therefore, the A protein must be exposed at both the inner and outer surfaces of the CP shell. Because the capsids of ssRNA phages contain holes at the 5-fold and 3-fold axes of symmetry that are large enough for the diffusion of RNA fragments, it was long believed that the A protein binds in proximity to these axes. However, it was recently shown in cryo-EM studies that the A protein actually replaces a single CP dimer [123,124]; as such, the virion actually contains 178 CP monomers.

Comparative investigations of MS2 VLPs and virions containing a copy of the A protein by SANS (small-angle neutron scattering) revealed some differences, particularly the presence of ‘thin' (preinfection) and ‘thick' (postinfection) capsids, which are not seen by crystallography [125]. The role of the A protein during virus assembly may involve the accumulation of tension that is later used to eject the genomic RNA and the A protein into a host cell.

Intrinsic Antigenicity and Immunogenicity

Species-specific virus-neutralizing antibody responses to RNA phages were studied in the late 1960s [126,127,128,129]. The MS2 phage was characterized as a T cell-dependent antigen that may also function as a T cell-independent antigen when used in high doses [130], with high efficacy in inducing T cell response [131]. However, no B cell epitopes have been mapped for virus-neutralizing antibodies on RNA phage capsids. General observations have shown the conformational nature of the B cell epitopes [our unpubl. data]. It was found that only a synthetic MS2 CP peptide spanning from positions 89 to 108 is capable of inhibiting phage neutralization by specific antiserum and of inducing the production of virus-neutralizing antibodies in rabbits [132] and guinea pigs [133]. Chemical conjugation of an N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) adjuvant to the 89-108 peptide also markedly increased the induction of virus-neutralizing antibodies in rabbits [134]. Although proper CP epitopes have not been mapped, the epitope-recognizing complementarity-determining region (CDR) peptides from a virus-neutralizing monoclonal antibody specific for phages fr, MS2, and GA were described and documented for their capability to neutralize the abovementioned phages [135]. Recently, CDRs from thermostable single-domain anti-MS2 antibodies obtained by the immunization of llamas were sequenced [136].

RNA Phage Coats as a VLP Carrier

Genetic Fusion as a First Step in the Development of RNA Phage VLP Carriers

Recombinant capsids of fr [137,138] and MS2 [139] were the first VLP carriers proposed for the presentation of foreign immunological epitopes on their surfaces by genetic fusion. To identify appropriate CP regions, oligonucleotide linkers encoding short aa sequences and containing convenient restriction sites were inserted into different regions of the fr CP [140]. Remarkably, this work was based on computer predictions of the spatial structure of the fr CP and was conducted before the first crystal structure of an RNA phage, namely that of the homologous MS2 capsid, had been resolved [83,84,85,86]. Recombinant fr CPs containing 2- to 12-aa-long additions to their N- or C-termini or insertions at position 50 in the RNA-binding region were capable of self-assembly, but this was not the case at positions 97-111 in the αA-helix [140]. The majority of other fr CP mutants demonstrated reduced self-assembly capabilities and formed either CP dimers (aa exchanges at residues 2, 10, 63, or 129) or both dimer and capsid structures (residue 2 or 69) [141]. The FG loop of the fr CP was also recognized as a potential target for insertions/replacements and was initially modified by a 4-aa-long deletion [142]. The deletion variant retained the ability to form capsids, although they displayed significantly reduced thermal stability. Furthermore, the 3D structures of the mutant capsids revealed that the modified loops were disordered near the 5-fold axis of symmetry and were too short to interact with each other [142]. Because of the high importance of the FG loop in capsid stability, further development of chimeras based on the implementation of FG loops was not pursued.

Vectors were constructed for the insertion of foreign sequences into codon position 2 of the fr CP-coding sequence in all possible reading frames [137]. When the preS1 epitope DPAFR from hepatitis B virus (HBV) was inserted as a marker at positions 2, 10, and 129, it appeared in all cases on the particle surface [137]. Attempts to introduce the 40-aa-long V3 loop from the human immunodeficiency virus 1 (HIV-1) gp120 protein into the N-terminus, at positions 10, 12, and 15, or into the FG loop led to unassembled products [K. Tars, unpubl. data].

Attempts to use the N-terminal β-hairpin exposed at the surface of the capsid, namely aa residues 15/16, allowed for the production of MS2 capsids bearing a number of different peptide sequences up to 24 aa residues in length [139]. Foreign epitopes exposed on these chimeras were found to be immunogenic in mice [139]. Mutational mapping revealed residues that are responsible for inter- and intramolecular contacts and therefore for the thermal stability of MS2 capsids [143].

The addition of the Flag octapeptide to the N-terminus or its insertion into the N-terminal β-hairpin of the MS2 CP prevented self-assembly and proper folding, respectively. However, genetic fusion of the Flag to a duplicated CP-encoding sequence resulted in the synthesis of a protein considerably more tolerant to the structural perturbations and mostly corrected the defects accompanying Flag peptide insertion [144]. The putative protective epitope T1, spanning 24 aa in length and derived from the immunodominant liver stage antigen-1 of the malaria parasite Plasmodium falciparum, was inserted at the tip of the N-terminal β-hairpin (between positions 15 and 16) of the MS2 CP [145].

fr VLPs have shown unusually high capacities as vectors, particularly when the addition of long segments of hamster polyomavirus VP1 to the N-terminus of the fr CP did not prevent VLP self-assembly [146]. When discovered, these findings markedly enhanced interest in using RNA phage coats as potent vaccine candidates.

However, the relatively low tolerance of fr- and MS2-based VLP vectors to long foreign insertions represents a clear limitation of these models. For example, the fr CP failed to form VLPs following the insertion of long HBV preS1 sequences [147]. To overcome this difficulty, Qβ protein A1, namely the C-terminal extension of the Qβ CP within the A1 protein, has been proposed as a site for foreign insertions [148,149]. Potentially, the 195-aa extension of the Qβ CP could be considered an ideal target for insertions. This region was found to contain elements that typically protrude as spike-like structures on the particle surface. Furthermore, the self-assembly capabilities of capsids with mutually exchanged extensions of the Qβ and SP CPs were confirmed experimentally [64]. A following mathematical prediction showed possible colinearity between the Qβ CP extension and the surface-located HBV preS sequence [148]. It is noteworthy that the crystal structure of the read-through domain from the Qβ A1 protein was recently determined at a resolution of 1.8 Å and revealed a fold that is unique among all proteins found in the protein data bank [150].

Qβ CP proteins with additions at their C-termini failed to form particles in most cases. However, such additions were incorporated into particles in the presence of a wt ‘helper' CP to form mixed, or mosaic, particles. Mosaic VLPs differ therefore from chimeric VLPs which are built from identical recombinant CP molecules, without any helper molecules. Such mosaic particles were constructed by either enhancing the level of UGA suppression in the presence of overexpressed suppressor tRNA [151] or by exchanging the UGA stop codon to a GGA sense codon and expressing the extended and helper forms of the Qβ CP from two separate genes. These genes were located either on the same plasmid or on two separate plasmids with different antibiotic resistance genes. Potential insertion sites were mapped by insertion of the 5-aa preS1 DPAFR model epitope and the 39-aa-long HIV-1 gp120 V3 loop [149]. After enhancing UGA suppression, mosaic particles were detected, but the proportion of A1 to helper CP in these particles dropped from 48 to 14% as the length of the A1 extension increased [152]. A model insertion of the preS1 epitope DPAFR located on the particle surface produced specific antigenicity and immunogenicity in mice [152]. The antibody response to the preS1 epitope was higher for self-assembled Qβ-preS1 VLPs than for a nonassembled Qβ-preS1 variant [153]. When the Qβ CP was modified to carry long HBV preS insertions (full-length preS, preS1, or preS2 alone) instead of the A1 extension, mosaic particles formed that had surface-exposed preS, but regular VLPs did not form without the presence of the Qβ CP as a helper [I. Cielens and R. Renhofa, unpubl. data].

On Qβ CP itself, the residues responsible for RNA recognition have been mapped [154,155]. This was helpful for the development of packaging and gene transfer technologies based on the Qβ phage model. The ability of the RNA phage CP to package RNA in vivo [156] demonstrated the potential of RNA phages as gene delivery vectors (see Nonvaccine Applications).

Surprisingly, icosahedral Qβ VLPs have been converted into rods after modification of the FG loop structure [157]. As mentioned above, the appearance of alternate VLP forms of RNA phages was further confirmed by the presence of rod-like structures in the case of the coassembly of phage fr and GA CPs [73].

The MS2 phage was found to be capable of accommodating short (pentapeptide) sequences added to the N-terminus of its CP within viable virions, although not all insertions were genetically stable [158]. Following well-known peptide display systems based on filamentous phages, a novel peptide display platform on MS2 VLPs was developed and successfully tested, including the identification of conformational epitopes [159,160].

As an experimental example of fusion technology, figure 5 compares RNA phage virions, recombinant VLPs, and chimeric VLPs carrying long foreign insertions by electron microscopy. It is remarkable that the surfaces of some insertion-containing VLPs differ considerably from the surfaces of unmodified VLPs by the appearance of distinct knobs that are presumably formed by the inserted sequences. Besides VLP applications, the phage fr CP was successfully used in its nonassembled variant for the fine mapping of epitopes, primarily of HBV-derived proteins[161,162,163,164,165,166].

Fig. 5

Electron micrographs of negatively stained AP205 virions (a), recombinant AP205 VLPs (b), chimeric AP205 VLPs carrying 151 aa residues of human interleukin-1β at the C-terminus (c), GA virions (d), recombinant GA VLPs (e), and chimeric GA VLPs carrying a 61-aa-long ZHER2:342 affibody at the C-terminus (f). VLPs are purified from the appropriate gene-expressing E. coli cells. For electron microscopy, the grids with the adsorbed particles were stained with aqueous solutions of 1% uranyl acetate (pH 4.5) or 2% phosphotungstic acid (pH 7.0) and examined with JEM-100C or JEM-1230 electron microscopes (Jeol Ltd., Tokyo, Japan) at 100 kV. Well-ordered knobs are clearly visible on the surfaces of the chimeric VLPs.

http://www.karger.com/WebMaterial/ShowPic/525635

Chemical Coupling to Further Develop VLP Technology

Chemical coupling of foreign oligopeptides to the surface of VLPs was developed as an alternative method to the genetic fusion of epitope-encoding sequences. Chemical coupling was initially applied to RNA phage Qβ VLPs in 2002 [167] by using an approach initially developed for another broadly used recombinant VLP, HBc (HBV core antigen) [167,168]. Model oligopeptides containing a free cysteine residue at the N-terminus were coupled to an exposed lysine residue on the Qβ VLP surface using the hetero-bifunctional cross-linker maleimidobenzoic acid sulfosuccinimidyl ester. The modified VLPs showed efficient induction of oligopeptide-specific antibodies in mice [167]. This chemical coupling approach initiated the development of a panel of experimental therapeutic vaccines (see early reviews by Bachmann and Dyer [169] and Dyer et al. [170], and a recent review by Bachmann and Jennings [171]). By following the lysine-cysteine oligopeptide coupling methodology, an experimental West Nile virus vaccine was constructed on an AP205 VLP platform [68].

Another chemical coupling approach was developed based on the rational design of modified MS2 VLPs that displayed a reactive thiol on the VLP surface as a result of a T15C substitution in the MS2 CP [172,173]. Cysteines are among the most useful functional groups found in proteins as they can bind a variety of metals and react with a large collection of organic reagents, and are therefore obvious targets for protein modification [172]. Two cysteine residues that are present in the wt MS2 CP are internally located and therefore relatively unreactive. Thiolated MS2 VLPs were chemically modified with fluorescein-5′-maleimide to create the first fluorescent nanoparticles [173].

Additional functionalization was achieved in a cell-free protein synthesis platform by the production of MS2 and Qβ VLPs with surface-exposed methionine analogues (azidohomoalanine and homopropargylglycine) containing azide and alkyne side chains [174]. Such VLPs can be used for one-step, direct conjugation schemes to display multiple ligands of interest. Using such technology, proteins including an antibody fragment and granulocyte-macrophage colony-stimulating factor, as well as nucleic acids and poly(ethylene glycol) chains, were displayed on the VLP surface using Cu(I) catalyzed click chemistry [174]. Surface functionalization methodology has not only been applied to the VLP surface but also to the interiors of MS2 VLPs by modification of tyrosine residues via a recently developed hetero-Diels-Alder bioconjugation reaction [175].

The preparation of histidine-tagged MS2 VLPs by the introduction of a His6 linker between CP codons 15 and 16 to simplify the purification of VLP-covered RNAs is another example of VLP surface functionalization [176]. Moreover, a set of advanced His6-tagged Qβ VLPs was generated, and their ability to complex metal-derivatized compounds was confirmed [177,178]. In parallel, VLP vector capacity for chemical coupling was broadened by the introduction of azide- or alkyne-containing unnatural amino acids, which was achieved by expression of the Qβ CP gene in a methionine auxotrophic strain of E. coli[179].

A highly specific approach for the further development of VLP vectors was achieved by the asymmetrization of Qβ VLPs after the introduction of a single copy of the maturation protein A2, which allowed the production of VLPs with a single unique modification [180].

Recently, a novel plug-and-display system was established for modular RNA phage VLP functionalization via further decoration of VLPs with peptides of interest [181,182]. The decoration of VLPs is based on the so-called bacterial superglue approach, namely on the ability of a peptide (SpyTag) and a protein (SpyCatcher) to form spontaneous covalent isopeptide bonds between lysine and aspartic acid residues under physiological conditions [183]. The SpyTag and SpyCatcher are split units of the Streptococcus pyogenes fibronectin-binding protein FbaB and can form a highly stable amide bond by an irreversible reaction that occurs within minutes [184]. The SpyTag or SpyCatcher sequences were genetically fused to the N- and/or C-terminus of the AP205 CP. After mixing modified AP205 VLPs with the correspondingly linked peptides, the quantitative covalent coupling of the peptides to the VLPs was observed [181,182].

Stability of VLPs

Efforts to improve the stability of natural RNA phage VLPs started with the development of a methodology that allowed the screening of bacteria for the synthesis of mutant MS2 CPs with altered assembly properties [185] and the selection of D11N variant CPs that formed virions more stable than the wt CP [186]. The introduction of interdisulfide bonds into the 5-fold axis of symmetry to cross-link MS2 VLPs improved their thermal stability to the level of that seen in Qβ VLPs, which possess natural intersubunit disulfide bonds [187]. In contrast, cross-linking at the 3-fold axis of symmetry resulted in variant CPs that were unable to self-assemble [187]. The development of an E. coli-based cell-free protein synthesis system opened a direct avenue for studying the role of disulfide bond formation in the stability of mutant MS2 VLPs in comparison to Qβ and HBc VLPs [188]. Through the construction of a set of Qβ CP mutants, it was found that disulfide linkages are the most important stabilizing elements in VLPs and that interdimer interactions are less important than intradimer interactions for Qβ VLP assembly [189].

Elucidation of the thermal stability of foreign epitope-carrying VLPs, such as the chimeric MS2 VLPs formed by single-chain dimers, in comparison to natural disulfide cross-linked PP7 VLPs [190] is of great importance for the further development of RNA phage-based nanotechnology. The genetic fusions of two copies of the MS2 [159], PP7 [191], and GA or Qβ [I. Cielens and A. Strods, unpubl. data] CPs resulted in a self-assembly-competent single-chain dimer that not only increased thermodynamic stability but also considerably improved tolerance to foreign insertions in the AB-loop. The resultant correctly assembled VLPs encapsidated mostly their ‘own' CP-encoding mRNAs.

Vaccines and Vaccine Candidates

Vaccines represent the most advanced field of the RNA phage VLP applications due to the excellent and well-established scaffold properties and structural tolerance to the decoration by foreign immunogenic sequences. Such decoration can be performed both genetically and chemically, and the VLP scaffold may provide foreign epitopes with a strong T cell response. Moreover, RNA phage VLPs can serve as nanocontainers that can encapsulate specific adjuvants, such as immunostimulatory oligodeoxynucleotides or CpGs, as TLR9 ligands [192]. RNA phage VLPs can also be packaged with single-stranded or double-stranded RNA fragments as TLR7 and TLR3 ligands, respectively [193]. Moreover, recombinant RNA phage VLPs contain encapsulated bacterial RNA, which may act as an adjuvant. Reviews on vaccine applications include articles discussing RNA phage VLPs among other VLP candidates [82,169,170,171,194,195,196,197,198,199,200,201,202] and articles focused either on RNA phage VLPs in general [203] or on the use of specific RNA phage species, such as MS2 VLPs, as vaccines [204].

Genetic Fusions

Table 1 contains a detailed list of the vaccine candidates that have been constructed from RNA phage VLPs using genetic fusion methodology. First, the success of an experimental human papilloma virus (HPV) vaccine based on PP7 single-chain-dimer VLPs [191,205,206,207,208,209] developed in preclinical studies [210] must be mentioned. A similar HPV vaccine candidate was constructed on MS2 single-chain-dimer VLPs and tested in preclinical studies [210,211]. Both PP7 and MS2 VLP-based vaccines were immunogenic, but the MS2-L2 VLPs induced a broader HPV-neutralizing antibody response. This is likely because of the structural context of L2 display on the VLPs, since L2 was displayed on the AB-loop of the PP7 CP, but at the N-terminus of the MS2 CP [191]. A review on HPV vaccine candidates, including RNA phage VLP-based vaccines, was recently published [212]. A malaria vaccine based on MS2 VLPs has also been reported as very promising [213,214]. As to the selection of optimal VLP carriers for such purposes, AP205 VLPs have demonstrated a high capacity and tolerance to foreign insertions [67]. Moreover, the AP205 VLPs represent good candidates for the construction of mosaic VLPs [215].

Table 1

Vaccines and vaccine candidates constructed on RNA phage VLPs and viable virions by genetic fusion methodology

http://www.karger.com/WebMaterial/ShowPic/525643

Chemical Coupling

The chemical coupling approach was validated by an impressive line of experimental therapeutic vaccines [169,171]. The idea of therapeutic vaccines is based on the assumption that VLP carriers can present surface-displayed self-antigens and to augment their ability to overcome the natural tolerance of the immune system toward self-proteins and to induce high levels of specific autoantibodies [216]. Initially, this approach was planned as a method to replace host-specific monoclonal antibodies in the treatment of acute and chronic diseases, starting with noninfectious diseases [169]. Therefore, the transition from passive administration of monoclonal antibodies to active vaccination against self-antigens was a logical step in drug development, focusing on affordable medicines and broader patient acceptance and regulatory compliance. The induction of autoantibodies might be beneficial under certain physiological conditions in order to remove unwanted excess of a particular self-antigen, such as angiotensin in the case of hypertension. Table 2 presents a detailed list of predominantly therapeutic vaccines and demonstrates the validity of this assumption.

Table 2

Vaccines and vaccine candidates constructed on RNA phage VLPs by chemical coupling methodology

http://www.karger.com/WebMaterial/ShowPic/525642

We included the well-known Qβ VLP-based allergy vaccine CYT003-QbG10 that contains an encapsulated CpG sequence, so-called QbG10, in table 2, although it does not carry any attached epitope [217,218,219,220,221]. However, this potentially successful vaccine initially originated from epitope-coupling methodology. Moreover, we included RNA phage VLPs carrying model epitope p33, which is derived from the lymphocytic choriomeningitis virus glycoprotein [222,223,224,225,226,227,228,229], and epitope D2, which is derived from Salmonella[230]. Although these are not actual vaccine candidates, the model epitopes have played a central role in the elucidation of the fine immunological mechanisms that govern responses to chimeric VLPs.

The display of small antigens, such as nicotine [231,232,233,234] or carbohydrate moieties [235,236], on RNA phage VLP surfaces is a novel approach that enabled the generation of strong immunological responses against nonpeptide antigens and paved the way for the development of experimental vaccines against nicotine addiction and cancer, respectively. We recommend a recent review on novel vaccines constructed on RNA phage VLPs [237] as well as special reviews on vaccines against allergies [238,239,240], Alzheimer disease [241], hypertension [242,243,244], influenza [245,246], malaria [247], and nicotine addiction [248,249,250,251,252].

Nonvaccine Applications

Attention is currently focused on the use of virus-based nanoparticles as potential scaffolds for novel biomaterials and as subjects for nanoscale engineering applications involving exposure to various chemical compounds [253,254,255,256].

Drug Delivery by Nanocontainers

Table 3 summarizes RNA phage VLP-based experimental approaches that could be classified as VLP packaging and targeting methodologies. Historically, the idea of encapsulation/targeting by RNA phage VLPs appeared in the early 1990s, only a few years after the vaccine/epitope display approaches described above. A first attempt at RNA phage nanocontainer-targeted drug delivery involved, first of all, encapsulation of a deglycosylated ricin A chain coupled to an RNA operator stem-loop and decoration of the MS2 VLPs by transferrin [257,258,259]. Such structures, called ‘synthetic virions' by the authors, demonstrated high toxicity to leukemia cells carrying transferrin receptor. A detailed review of these and similar pioneering experiments was published in 2002 [260]. Another detailed review devoted to anticancer perspectives of nanoparticles filled with siRNA was recently published [261].

Table 3

The RNA phage VLPs as models for nanocontainer packaging and decoration with addressing/targeting/delivery purposes

http://www.karger.com/WebMaterial/ShowPic/525641

The next step in the development of VLP packaging/targeting technology included the chemical coupling of putative cargo and targeting molecules to the outer and inner surfaces of VLPs, respectively [175,262,263,264,265,266,267]. It has been demonstrated that MS2 VLPs can be conjugated to peptides recognizing human hepatocellular carcinoma cells and can be loaded with vastly different types of cargo, including low molecular weight chemotherapeutic drugs, siRNA cocktails, protein toxins and nanoparticles, resulting in the selective killing of target cells [268]. The packaging of Qβ VLPs with immunostimulatory CpG sequences led not only to the development of potential allergy vaccines (see above) but also strongly contributed to the general understanding of the mechanics of oligodeoxynucleotide-induced stimulation [217,218,219,220,221,222,223,224,225,226,227,228,229,269,270].

Imaging

The use of imaging agents in combination with RNA phage VLPs has contributed to the high-resolution and noninvasive visualization of these particles, as well as to the potential treatment of diseases [254]. The RNA phage VLP-based applications that have been developed as imaging technologies are compiled in table 4. The first studies on the generation of nanoparticles for magnetic resonance imaging applications and the first comparisons of interior versus exterior cargo strategies appeared in the mid 2000s [271,272]. Following these reports, MS2 VLPs were loaded with positron emission tomography radiolabels [273]. To date, MS2 phages and VLPs have played a leading role in bioimaging studies.

Table 4

The bioimaging agents on the basis of RNA phage VLPs and virions

http://www.karger.com/WebMaterial/ShowPic/525640

Armored Polynucleotides for Diagnostic Applications

The ‘armored' nucleic acids are useful as noninfectious, easily available reagents for the quality control in the diagnosis of pathogenic viruses like HCV (hepatitis C virus). As an example of ‘armored RNA' technology, MS2 VLPs were made to perform in vivo encapsidation of a desired RNA, which was accomplished by including the MS2 operator sequence on the RNA molecule to enable its packaging. The armored RNA was therefore protected from RNase digestion [274]. Recently, the creation of armored dsDNA using HBV and HPV particles was accomplished on the basis of previous work using MS2 VLPs [275]. Armored RNAs have multiple uses, such as for the detection of HCV, severe acute respiratory syndrome coronavirus, and influenza virus RNA [276] or for the creation of unique RNA molecules harboring both tRNA and mRNA functions [277]. Perspectives on the production and practical use of MS2 VLPs for routine diagnostics including food quality control were discussed in a recent review [278].

Future Perspectives

The next milestones for the development of the RNA phage VLP field are presented in figure 6. The major tendency provides the combination of both (i) decoration of the VLP scaffolds with molecules of interest and (ii) packaging of foreign material into VLP nanocontainers.

Fig. 6

General milestones of the development of RNA phage VLPs as nanotools. The 3D structure of the MS2 phage is presented at the top.

http://www.karger.com/WebMaterial/ShowPic/525634

Vaccine Design

Vaccineswill remain a classic area for the application of RNA phage VLPs [279]. For example, clear progress in vaccine formulation and storage was achieved through a MS2 VLP-based papillomavirus vaccine [280]. RNA phage CP properties can be used in combination with other possible vaccine carriers, such as retroviral platforms, with a special goal to improve RNA packaging and delivery [281].

Peptide Display

MS2 VLPs [160] and Qβ phage [32] offer favorable alternatives to filamentous bacteriophages for the display of immunologically active peptides. Recently, a tumor-associated antigen was identified using MS2 peptide-display technology [282], confirming the importance of such a methodology for future studies.

Nanomachines

RNA phage VLPs are regarded as potential components of future nanomachines, which is a general term for a machine ranging in size from 1 nm to 1 μm. Perspectives on the revolutionary nanoscale engineering of RNA phage VLPs as natural prefabricated scaffolds to contain molecules in precisely defined arrays were described in a recent review [253]. The future of VLP-derived materials [for chemical strategies and details of VLP bioconjugation technologies, see [283]] is quite impressive because the number of methods that can be used to change both the interior and exterior surfaces of capsids by the incorporation of organic and inorganic compounds is unlimited. Further development of VLPs with defined antigenic and immunogenic properties, as well as VLPs with improved packaging and targeting capabilities, will create novel viral nanotechnology applications and is expected to produce nanomachines with rationally designed characteristics. For example, an interesting new approach is exemplified by the use of DNA as a scaffold to arrange MS2 VLPs into one-dimensional arrays with precise nanoscale positioning [284]. Such bioinspired plasmonic nanostructures may provide a flexible design base for manipulating photonic excitation and photoemission [285].

Search for New RNA Phage Vectors

The clear differences that exist in RNA phage VLP structures, stabilities, and reconstruction capacities have provoked extensive studies aimed at identifying novel members of the Leviviridae family. Out of such efforts, 19 new genomes of icosahedral RNA phages [286], genomes from the phages M [287], C-1 and HgalI [288], DL52 and DL54 [289], from a so-called JS-like group [290] and of the phages EC and MB [291], have been described.

A recent survey of metagenomic databases revealed 158 partial single-stranded RNA phage genome sequences belonging to about 120 distinct phylotypes [292]. Sixty-six of the genomes contained a putative open reading frame predicted to be the CP [292]. Novel RNA phage sequences were present in samples collected from a range of ecological niches worldwide, including invertebrates and extreme microbial sediment, demonstrating that they are more widely distributed than previously recognized [292]. These genomes are expected to undergo studies of CP gene expression as well as elucidation of their 3D capsid structures, and will potentially serve in new applications.

Structural Studies

3D structural investigations have revealed unexpected capabilities of RNA phage capsids, such as their ability to transform into T = 1 [77] or rod-like [157] structures. Moreover, such studies have contributed worthwhile information towards understanding protein folding and virus assembly [293]. Additional important directions for future studies involve the elucidation of VLP surface properties in the context of the presence of internal RNA, as reported previously [294], and/or the external display of foreign sequences of different origins, such as oligonucleotides, peptides, sugars, and metal ions. Such studies would be helpful for the prediction of VLP characteristics in the context of aqueous and nonaqueous media, as well as under different biological conditions, which should facilitate the use of these particles as vaccines and/or gene therapy tools.

Acknowledgements

We thank Dr. Maija Bundule, Dr. Indulis Cielens, Dr. Dzidra Dreilina, Dr. Juris Jansons, Dr. Andris Kazaks, Dr. Janis Klovins, Dr. Janis Rumnieks, Dr. Dace Skrastina, Dr. Irina Sominskaya, Dr. Arnis Strods, Dr. Alexander Tsimanis, Dr. Inta Vasiljeva, Dr. Tatjana Voronkova, and Ms. Inara Akopjana (Riga) for their contributions and sharing of unpublished data. We are grateful to Prof. Dr. Rüdiger Schmitt (Regensburg) for the first N-terminal aa sequence of the AP205 CP and to Prof. Dr. Wolfram H. Gerlich (Giessen) for his critical reading of the manuscript and helpful comments.


References

  1. Loeb T, Zinder ND: A bacteriophage containing RNA. Proc Natl Acad Sci USA 1961;47:282-289.
  2. Davis J, Strauss J, Sinsheimer R: Bacteriophage MS2: another RNA phage. Science 1961;134:1427.
  3. Paranchych W, Graham AF: Isolation and properties of an RNA-containing bacteriophage. J Cell Comp Physiol 1962;60:199-208.
  4. Marvin DA, Hoffmann-Berling H: Physical and chemical properties of 2 new small bacteriophages. Nature 1963;197:517-518.
    External Resources
  5. Hofschneider PH: Untersuchungen über ‘kleine' E. coli K12 Bacteriophagen. I. Mitt.: Die Isolierung und einige Eigenschaften der ‘kleinen' Bacteriophagen M12, M13 und M20. Z Naturforsch 1963;18b:203-205.
    External Resources
  6. Watanabe I: Persistent infection with an RNA bacteriophage. Nippon Rinsho 1964;22:243-251.
  7. Gren EJ: Regulatory Mechanisms of RNA Bacteriophage Replication (in Russian). Riga, Zinatne, 1974.
  8. Zinder ND (ed): RNA Phages. Cold Spring Harbor, Cold Spring Harbor Laboratory, 1975.
  9. Zinder ND: Portraits of viruses: RNA phage. Intervirology 1980;13:257-270.
  10. Miyake T, Shiba T, Sakurai T, Watanabe I: Isolation and properties of two new RNA phages SP and FI. Jpn J Microbiol 1969;13:375-382.
  11. Aoi T, Furuse K, Watanabe I, Osawa S: Isolation and properties of temperature-sensitive mutants of group II RNA phage GA (in Japanese). Uirusu 1973;23:19-28.
  12. Schmidt JM, Stanier RY: Isolation and characterization of bacteriophages active against stalked bacteria. J Gen Microbiol 1965;39:95-107.
  13. Bradley D: The structure and infective process of a Pseudomonas aeruginosa bacteriophage containing ribonucleic acid. J Gen Microbiol 1966;45:83-96.
  14. Olsen RH, Thomas DD: Characteristics and purification of PRR1, an RNA phage specific for the broad host range Pseudomonas R1822 drug resistance plasmid. J Virol 1973;12:1560-1567.
    External Resources
  15. Coffi H: Lysotypie des Acinetobacter; MSc thesis, Laval University, Quebec, 1995.
  16. Klovins J, Overbeek GP, van den Worm SH, Ackermann HW, van Duin J: Nucleotide sequence of a ssRNA phage from Acinetobacter: kinship to coliphages. J Gen Virol 2002;83:1523-1533.
  17. International Committee on Taxonomy of Viruses: Virus Taxonomy: 2014 Release. EC 46, Montreal, Canada, July 2014. http://ictvonline.org/virusTaxonomy.asp.
  18. Inokuchi Y, Hirashima A. Watanabe I: Comparison of the nucleotide sequences at the 3′-terminal region of RNAs from RNA coliphages. J Mol Biol 1982;158:711-730.
  19. NCBI: Taxonomy browser. http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11989.
  20. Krueger RG: Serological relatedness of the ribonucleic acid-containing coliphages. J Virol 1969;4:567-573.
    External Resources
  21. Furuse K: Distribution of coliphages in the environment: general considerations; in Goyal SM, Gerba CP, Bitton G (eds): Phage Ecology. New York, John Wiley, 1987, pp 87-124.
  22. Miyake T, Haruna I, Shiba T, Ito YH, Yamane K: Grouping of RNA phages based on the template specificity of their RNA replicases. Proc Natl Acad Sci USA 1971;68:2022-2024.
  23. Hsu FC, Shieh YS, van Duin J, Beekwilder MJ, Sobsey MD: Genotyping male-specific RNA coliphages by hybridization with oligonucleotide probes. Appl Environ Microbiol 1995;61:3960-3966.
    External Resources
  24. Friedman SD, Cooper EM, Calci KR, Genthner FJ: Design and assessment of a real time reverse transcription-PCR method to genotype single-stranded RNA male-specific coliphages (family Leviviridae). J Virol Methods 2011;173:196-202.
  25. Guan D, Joerger RD, Kniel KE, Calci KR, Hicks DT, Pivarnik LF, Hoover DG: Effect of high hydrostatic pressure on four genotypes of F-specific RNA bacteriophages. J Appl Microbiol 2007;102:51-56.
  26. Muniesa M, Payan A, Moce-Llivina L, Blanch AR, Jofre J: Differential persistence of F-specific RNA phage subgroups hinders their use as single tracers for faecal source tracking in surface water. Water Res 2009;43:1559-1564.
  27. Hartard C, Rivet R, Banas S, Gantzer C: Occurrence of and sequence variation among F-specific RNA bacteriophage subgroups in feces and wastewater of urban and animal origins. Appl Environ Microbiol 2015;81:6505-6515.
  28. Weiner AM, Weber K: Natural read-through at the UGA termination signal of Qβ coat protein cistron. Nat New Biol 1971;234:206-209.
  29. Hofstetter H, Monstein HJ, Weissmann C: The readthrough protein A1 is essential for the formation of viable Qβ particles. Biochim Biophys Acta 1974;374:238-251.
  30. Engelberg-Kulka H, Dekel L, Israeli-Reches M: Streptomycin-resistant Escherichia coli mutant temperature sensitive for the production of Qβ-infective particles. J Virol 1977;21:1-6.
    External Resources
  31. Engelberg-Kulka H, Israeli-Reches M, Dekel L, Friedmann A: Qβ-defective particles produced in a streptomycin-resistant Escherichia coli mutant. J Virol 1979;29:1107-1117.
    External Resources
  32. Skamel C, Aller SG, Bopda Waffo A: In vitro evolution and affinity-maturation with coliphage Qβ display. PLoS One 2014;9:e113069.
  33. Bollback JP, Huelsenbeck JP: Phylogeny, genome evolution, and host specificity of single-stranded RNA bacteriophage (family Leviviridae). J Mol Evol 2001;52:117-128.
  34. Goessens WH, Driessen AJ, Wilschut J, van Duin J: A synthetic peptide corresponding to the C-terminal 25 residues of phage MS2 coded lysis protein dissipates the protonmotive force in Escherichia coli membrane vesicles by generating hydrophilic pores. EMBO J 1988;7:867-873.
    External Resources
  35. Pierrel J: An RNA phage Lab: MS2 in Walter Fiers' laboratory of molecular biology in Ghent, from genetic code to gene and genome, 1963-1976. J Hist Biol 2012;45:109-138.
  36. Fiers W, Contreras R, Duerinck F, Haegeman G, Iserentant D, Merregaert J, Min Jou W, Molemans F, Raeymaekers A, van den Berghe A, Volckaert G, Ysebaert M: Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene. Nature 1976;260:500-507.
  37. Crowther RA, Amos LA, Finch JT: Three-dimensional image reconstructions of bacteriophages R17 and f2. J Mol Biol 1975;98:631-635.
  38. Caspar DL, Klug A: Physical principles in the construction of regular viruses. Cold Spring Harb Symp Quant Biol 1962;27:1-24.
  39. Coleman J, Hirashima A, Inokuchi Y, Green PJ, Inouye M: A novel immune system against bacteriophage infection using complementary RNA (micRNA). Nature 1985;315:601-603.
  40. Hirashima A, Sawaki S, Inokuchi Y, Inouye M: Engineering of the mRNA-interfering complementary RNA immune system against viral infection. Proc Natl Acad Sci USA 1986;83:7726-7730.
  41. Krivisky AS, Cherban TP: Comparative study of the lethal and mutagenic action of chemical agents and radiations on the MS2 bacteriophage and its infectious RNA (in French). Arch Roum Pathol Exp Microbiol 1969;28:866-876.
    External Resources
  42. Wigginton KR, Pecson BM, Sigstam T, Bosshard F, Kohn T: Virus inactivation mechanisms: impact of disinfectants on virus function and structural integrity. Environ Sci Technol 2012;46:12069-12078.
  43. Kimmitt PT, Redway KF: Evaluation of the potential for virus dispersal during hand drying: a comparison of three methods. J Appl Microbiol 2016;120:478-486.
  44. Tomas ME, Kundrapu S, Thota P, Sunkesula VC, Cadnum JL, Mana TS, Jencson A, O'Donnell M, Zabarsky TF, Hecker MT, Ray AJ, Wilson BM, Donskey CJ: Contamination of health care personnel during removal of personal protective equipment. JAMA Intern Med 2015;175:1904-1910.
  45. Verbyla ME, Mihelcic JR: A review of virus removal in wastewater treatment pond systems. Water Res 2015;71:107-124.
  46. McAlister M, Aranha H, Larson R: Use of bacteriophages as surrogates for mammalian viruses. Dev Biol (Basel) 2004;118:89-98.
    External Resources
  47. Sinclair RG, Rose JB, Hashsham SA, Gerba CP, Haas CN: Criteria for selection of surrogates used to study the fate and control of pathogens in the environment. Appl Environ Microbiol 2012;78:1969-1977.
  48. Liu J, Ochieng C, Wiersma S, Ströher U, Towner JS, Whitmer S, Nichol ST, Moore CC, Kersh GJ, Kato C, Sexton C, Petersen J, Massung R, Hercik C, Crump JA, Kibiki G, Maro A, Mujaga B, Gratz J, Jacob ST, Banura P, Scheld WM, Juma B, Onyango CO, Montgomery JM, Houpt E, Fields B: Development of a TaqMan array card for acute-febrile-illness outbreak investigation and surveillance of emerging pathogens, including Ebola virus. J Clin Microbiol 2016;54:49-58.
  49. Lodish HF: Translational control of protein synthesis: the early years. J Biol Chem 2012;287:36528-36535.
  50. Pumpen PP, Gren EJ: Role of protein synthesis in the regulation of replication of RNA-containing bacteriophages (in Russian). Dokl Akad Nauk SSSR 1975;224:246-248.
    External Resources
  51. Pumpen P, Bauman V, Dishler A, Gren EJ: Control of replication in RNA bacteriophages. J Virol 1978;28:725-735.
    External Resources
  52. Lampasona AA, Czaplinski K: RNA voyeurism: a coming of age story. Methods 2016;98:10-17.
  53. Bensidoun P, Raymond P, Oeffinger M, Zenklusen D: Imaging single mRNAs to study dynamics of mRNA export in the yeast Saccharomyces cerevisiae. Methods 2016;98:104-114.
  54. Gong C, Maquat LE: Affinity purification of long noncoding RNA-protein complexes from formaldehyde cross-linked mammalian cells. Methods Mol Biol 2015;1206:81-86.
  55. Hocine S, Raymond P, Zenklusen D, Chao JA, Singer RH: Single-molecule analysis of gene expression using two-color RNA labeling in live yeast. Nat Methods 2013;10:119-121.
  56. Bardwell VJ, Wickens M: Purification of RNA and RNA-protein complexes by an R17 coat protein affinity method. Nucleic Acids Res 1990;18:6587-6594.
  57. Dahlman JE, Abudayyeh OO, Joung J, Gootenberg JS, Zhang F, Konermann S: Orthogonal gene knockout and activation with a catalytically active Cas9 nuclease. Nat Biotechnol 2015;33:1159-1161.
  58. Remaut E, Waele PD, Marmenout A, Stanssens P, Fiers W: Functional expression of individual plasmid-coded RNA bacteriophage MS2 genes. EMBO J 1982;1:205-209.
    External Resources
  59. Kastelein RA, Berkhout B, Overbeek GP, van Duin J: Effect of the sequences upstream from the ribosome-binding site on the yield of protein from the cloned gene for phage MS2 coat protein. Gene 1983;23:245-254.
  60. Kozlovskaia TM, Pumpen PP, Dreilinia DE, Tsimanis AIu, Ose VP,Tsibinogin VV, Gren EJ: Formation of capsid-like structures as a result of expression of the cloned gene of the envelope protein of the RNA-containing bacteriophage fr (in Russian). Dokl Akad Nauk SSSR 1986;287:452-455.
    External Resources
  61. Adhin MR, Hirashima A, van Duin J: Nucleotide sequence from the ssRNA bacteriophage JP34 resolves the discrepancy between serological and biophysical classification. Virology 1989;170:238-242.
  62. Ni CZ, White CA, Mitchell RS, Wickersham J, Kodandapani R, Peabody DS, Ely KR: Crystal structure of the coat protein from the GA bacteriophage: model of the unassembled dimer. Protein Sci 1996;5:2485-2493.
  63. Kozlovska TM, Cielens I, Dreilina D, Dislers A, Baumanis V, Ose V, Pumpens P: Recombinant RNA phage Qβ capsid particles synthesized and self-assembled in Escherichia coli. Gene 1993;137:133-137.
  64. Priano C, Arora R, Butke J, Mills DR: A complete plasmid-based complementation system for RNA coliphage Qβ: three proteins of bacteriophages Qβ (group III) and SP (group IV) can be interchanged. J Mol Biol 1995;249:283-297.
  65. Lim F, Downey TP, Peabody DS: Translational repression and specific RNA binding by the coat protein of the Pseudomonas phage PP7. J Biol Chem 2001;276:22507-22513.
  66. Caldeira JC, Peabody DS: Stability and assembly in vitro of bacteriophage PP7 virus-like particles. J Nanobiotechnol 2007;5:10.
  67. Tissot AC, Renhofa R, Schmitz N, Cielens I, Meijerink E, Ose V, Jennings GT, Saudan P, Pumpens P, Bachmann MF: Versatile virus-like particle carrier for epitope based vaccines. PLoS One 2010;5:e9809.
  68. Spohn G, Jennings GT, Martina BE, Keller I, Beck M, Pumpens P, Osterhaus AD, Bachmann MF: A VLP-based vaccine targeting domain III of the West Nile virus E protein protects from lethal infection in mice. Virol J 2010;7:146.
  69. Persson M, Tars K, Liljas L: The capsid of the small RNA phage PRR1 is stabilized by metal ions. J Mol Biol 2008;383:914-922.
  70. Plevka P, Kazaks A, Voronkova T, Kotelovica S, Dishlers A, Liljas L, Tars K: The structure of bacteriophage φCb5 reveals a role of the RNA genome and metal ions in particle stability and assembly. J Mol Biol 2009;391:635-647.
  71. Spirin AS, Baranov VI, Ryabova LA, Ovodov SY, Alakhov YB: A continuous cell-free translation system capable of producing polypeptides in high yield. Science 1988;242:1162-1164.
  72. Bundy BC, Franciszkowicz MJ, Swartz JR: Escherichia coli-based cell-free synthesis of virus-like particles. Biotechnol Bioeng 2008;100:28-37.
  73. Rumnieks J, Ose V, Tars K, Dislers A, Strods A, Cielens I, Renhofa R: Assembly of mixed rod-like and spherical particles from group I and II RNA bacteriophage coat proteins. Virology 2009;391:187-194.
  74. Legendre D, Fastrez J: Production in Saccharomyces cerevisiae of MS2 virus-like particles packaging functional heterologous mRNAs. J Biotechnol 2005;117:183-194.
  75. Freivalds J, Dislers A, Ose V, Skrastina D, Cielens I, Pumpens P, Sasnauskas K, Kazaks A: Assembly of bacteriophage Qβ virus-like particles in yeast Saccharomyces cerevisiae and Pichia pastoris. J Biotechnol 2006;123:297-303.
  76. Freivalds J, Rumnieks J, Ose V, Renhofa R, Kazaks A: High-level expression and purification of bacteriophage GA virus-like particles from yeast Saccharomyces cerevisiae and Pichia pastoris. Acta Universitatis Latviensis Biol 2008;745:75-85.
  77. Freivalds J, Kotelovica S, Voronkova T, Ose V, Tars K, Kazaks A: Yeast-expressed bacteriophage-like particles for the packaging of nanomaterials. Mol Biotechnol 2014;56:102-110.
  78. Rossmann MG: Structure of viruses: a short history. Q Rev Biophys 2013;46:133-180.
  79. Schwartz FM, Zinder ND: Crystalline aggregates in bacterial cells infected with the RNA bacteriophage f2. Virology 1963;21:276-278.
  80. de Petris S, Nava G: Sex specific bacteriophages of E. coli K12. II. Electron microscope observations on the structure and intracellular multiplication of bacteriophage µ2. Giorn Microbiol 1963;11:1-7.
  81. Franklin RM, Granboulan N: Ultrastructure of Escherichia coli cells infected with bacteriophage R17. J Bacteriol 1966;91:834-848.
    External Resources
  82. Pumpens P, Grens E: Artificial genes for chimeric virus-like particles; in Khudyakov YE, Fields HA (eds): Artificial DNA. Methods and Applications. Boca Raton, CRC Press LLC, 2002, pp 249-327.
    External Resources
  83. Valegård K, Unge T, Montelius I, Strandberg B, Fiers W: Purification, crystallization and preliminary X-ray data of the bacteriophage MS2. J Mol Biol 1986;190:587-591.
  84. Valegård K, Liljas L, Fridborg K, Unge T: The three-dimensional structure of the bacterial virus MS2. Nature 1990;345:36-41.
  85. Valegård K, Liljas L, Fridborg K, Unge T: Structure determination of the bacteriophage MS2. Acta Crystallogr B 1991;47:949-960.
  86. Golmohammadi R, Valegård K, Fridborg K, Liljas L: The refined structure of bacteriophage MS2 at 2.8 Å resolution. J Mol Biol 1993;234:620-639.
  87. Stonehouse NJ, Valegård K, Golmohammadi R, van den Worm S, Walton C, Stockley PG, Liljas L: Crystal structures of MS2 capsids with mutations in the subunit FG loop. J Mol Biol 1996;256:330-339.
  88. Min Jou W, Raeymaekers A, Fiers W: Crystallization of bacteriophage MS2. Eur J Biochem 1979;102:589-594.
  89. Bundule M, Pumpens P, Ose V, Valegård K, Liljas L: Crystallization of bacteriophage fr and its recombinant capsids. J Mol Biol 1993;232:1005-1006.
  90. Liljas L, Fridborg K, Valegård K, Bundule M, Pumpens P: Crystal structure of bacteriophage fr capsids at 3.5 Å resolution. J Mol Biol 1994;244:279-290.
  91. Tars K, Bundule M, Fridborg K, Liljas L: The crystal structure of bacteriophage GA and a comparison of bacteriophages belonging to the major groups of Escherichia coli leviviruses. J Mol Biol 1997;271:759-773.
  92. Valegård K, Fridborg K, Liljas L: Crystallization and preliminary X-ray diffraction studies of the bacteriophage Qβ. Acta Crystallogr D Biol Crystallogr 1994;50:105-109.
  93. Golmohammadi R, Fridborg K, Bundule M, Valegård K, Liljas L: The crystal structure of bacteriophage Qβ at 3.5 Å resolution. Structure 1996;4:543-554.
  94. Tars K, Fridborg K, Bundule M, Liljas L: Structure determination of bacteriophage PP7 from Pseudomonas aeruginosa: from poor data to a good map. Acta Crystallogr D Biol Crystallogr 2000;56:398-405.
  95. Tars K, Fridborg K, Bundule M, Liljas L: The three-dimensional structure of bacteriophage PP7 from Pseudomonas aeruginosa at 3.7-Å resolution. Virology 2000;272:331-337.
  96. Lim F, Peabody DS: RNA recognition site of PP7 coat protein. Nucleic Acids Res 2002;30:4138-4144.
  97. Nap RJ, Božič AL, Szleifer I, Podgornik R: The role of solution conditions in the bacteriophage PP7 capsid charge regulation. Biophys J 2014;107:1970-1979.
  98. Hull R: The stabilization of the particles of turnip rosette virus and of other members of the southern bean mosaic virus group. Virology 1977;79:58-66.
  99. Shishovs M, Rumnieks J, Diebholder C, Jaudzems K, Kazaks A, Pintacuda G, Koning R, Tars K: Structure of AP205 coat protein reveals circular permutation in ssRNA bacteriophage. J Mol Biol. 2016;428:4267-4279.
  100. Ni CZ, Syed R, Kodandapani R, Wickersham J, Peabody DS, Ely KR: Crystal structure of the MS2 coat protein dimer: implications for RNA binding and virus assembly. Structure 1995;3:255-263.
  101. Peabody DS, Lim F: Complementation of RNA binding site mutations in MS2 coat protein heterodimers. Nucleic Acids Res 1996;24:2352-2359.
  102. Plevka P, Tars K, Liljas L: Structure and stability of icosahedral particles of a covalent coat protein dimer of bacteriophage MS2. Protein Sci 2009;18:1653-1661.
  103. Plevka P, Tars K, Liljas L: Crystal packing of a bacteriophage MS2 coat protein mutant corresponds to octahedral particles. Protein Sci 2008;17:1731-1739.
  104. Valegård K, Murray JB, Stockley PG, Stonehouse NJ, Liljas L: Crystal structure of an RNA bacteriophage coat protein-operator complex. Nature 1994;371:623-626.
  105. Stockley PG, Stonehouse NJ, Murray JB, Goodman ST, Talbot SJ, Adams CJ, Liljas L, Valegård K: Probing sequence-specific RNA recognition by the bacteriophage MS2 coat protein. Nucleic Acids Res 1995;23:2512-2518.
  106. Valegård K, Murray JB, Stonehouse NJ, van den Worm S, Stockley PG, Liljas L: The three-dimensional structures of two complexes between recombinant MS2 capsids and RNA operator fragments reveal sequence-specific protein-RNA interactions. J Mol Biol 1997;270:724-738.
  107. Lago H, Fonseca SA, Murray JB, Stonehouse NJ, Stockley PG: Dissecting the key recognition features of the MS2 bacteriophage translational repression complex. Nucleic Acids Res 1998;26:1337-1344.
  108. van den Worm SH, Stonehouse NJ, Valegård K, Murray JB, Walton C, Fridborg K, Stockley PG, Liljas L: Crystal structures of MS2 coat protein mutants in complex with wild-type RNA operator fragments. Nucleic Acids Res 1998;26:1345-1351.
  109. Peabody DS, Chakerian A: Asymmetric contributions to RNA binding by the Thr45 residues of the MS2 coat protein dimer. J Biol Chem 1999;274:25403-25410.
  110. Lim F, Spingola M, Peabody DS: Altering the RNA binding specificity of a translational repressor. J Biol Chem 1994;269:9006-9010.
    External Resources
  111. Lim F, Peabody DS: Mutations that increase the affinity of a translational repressor for RNA. Nucleic Acids Res 1994;22:3748-3752.
  112. Convery MA, Rowsell S, Stonehouse NJ, Ellington AD, Hirao I, Murray JB, Peabody DS, Phillips SE, Stockley PG: Crystal structure of an RNA aptamer-protein complex at 2.8 Å resolution. Nat Struct Biol 1998;5:133-139.
  113. Rowsell S, Stonehouse NJ, Convery MA, Adams CJ, Ellington AD, Hirao I, Peabody DS, Stockley PG, Phillips SE: Crystal structures of a series of RNA aptamers complexed to the same protein target. Nat Struct Biol 1998;5:970-975.
  114. Grahn E, Stonehouse NJ, Murray JB, van den Worm S, Valegård K, Fridborg K, Stockley PG, Liljas L: Crystallographic studies of RNA hairpins in complexes with recombinant MS2 capsids: implications for binding requirements. RNA 1999;5:131-138.
  115. Horn WT, Convery MA, Stonehouse NJ, Adams CJ, Liljas L, Phillips SE, Stockley PG: The crystal structure of a high affinity RNA stem-loop complexed with the bacteriophage MS2 capsid: further challenges in the modeling of ligand-RNA interactions. RNA 2004;10:1776-1782.
  116. Persson M, Tars K, Liljas L: PRR1 coat protein binding to its RNA translational operator. Acta Crystallogr D Biol Crystallogr 2013;69:367-372.
  117. Chao JA, Patskovsky Y, Almo SC, Singer RH: Structural basis for the coevolution of a viral RNA-protein complex. Nat Struct Mol Biol 2008;15:103-105.
  118. Rumnieks J, Tars K: Crystal structure of the bacteriophage Qβ coat protein in complex with the RNA operator of the replicase gene. J Mol Biol 2014;426:1039-1049.
  119. Koning R, van den Worm S, Plaisier JR, van Duin J, Pieter Abrahams J, Koerten H: Visualization by cryo-electron microscopy of genomic RNA that binds to the protein capsid inside bacteriophage MS2. J Mol Biol 2003;332:415-422.
  120. Toropova K, Basnak G, Twarock R, Stockley PG, Ranson NA: The three-dimensional structure of genomic RNA in bacteriophage MS2: implications for assembly. J Mol Biol 2008;375:824-836.
  121. Rolfsson Ó, Middleton S, Manfield IW, White SJ, Fan B, Vaughan R, Ranson NA, Dykeman E, Twarock R, Ford J, Cheng Kao C, Stockley PG: Direct evidence for packaging signal-mediated assembly of bacteriophage MS2. J Mol Biol 2016;428:431-448.
  122. Stockley PG, White SJ, Dykeman E, Manfield I, Rolfsson O, Patel N, Bingham R, Barker A, Wroblewski E, Chandler-Bostock R, Weiß EU, Ranson NA, Tuma R, Twarock R: Bacteriophage MS2 genomic RNA encodes an assembly instruction manual for its capsid. Bacteriophage 2016;6:e1157666.
  123. Dent KC, Thompson R, Barker AM, Hiscox JA, Barr JN, Stockley PG, Ranson NA: The asymmetric structure of an icosahedral virus bound to its receptor suggests a mechanism for genome release. Structure 2013;21:1225-1234.
  124. Koning RI, Gomez-Blanco J, Akopjana I, Vargas J, Kazaks A, Tars K, Carazo JM, Koster AJ: Asymmetric cryo-EM reconstruction of phage MS2 reveals genome structure in situ. Nat Commun 2016;7:12524.
  125. Kuzmanovic DA, Elashvili I, Wick C, O'Connell C, Krueger S: The MS2 coat protein shell is likely assembled under tension: a novel role for the MS2 bacteriophage A protein as revealed by small-angle neutron scattering. J Mol Biol 2006;355:1095-1111.
  126. Rowlands DT Jr: Precipitation and neutralization of bacteriophage f2 by rabbit antibodies. J Immunol 1967;98:958-964.
    External Resources
  127. Rappaport I: An analysis of the inactivation of MS2 bacteriophage with antiserum. J Gen Virol 1970;6:25-32.
  128. Rohrmann GF, Krueger RG: Precipitation and neutralization of bacteriophage MS-2 by rabbit antibodies. J Immunol 1970;104:353-358.
    External Resources
  129. Krueger RG: Effect of antigenic stimulation on the specificity of antibody produced by rabbits immunized with bacteriophage MS-2. J Immunol 1970;104:1117-1123.
    External Resources
  130. Snippe H, de Reuver MJ, Belder M, Willers JM: Bacteriophage MS-2 in the immune response. Int Arch Allergy Appl Immunol 1976;50:111-122.
  131. Langbeheim H, Teitelbaum D, Arnon R: Cellular immune response toward MS-2 phage and a synthetic fragment of its coat protein. Cell Immunol 1978;38:193-197.
  132. Langbeheim H, Arnon R, Sela M: Antiviral effect on MS-2 coliphage obtained with a synthetic antigen. Proc Natl Acad Sci USA 1976;73:4636-4640.
  133. Langbeheim H, Arnon R, Sela M: Adjuvant effect of a peptidoglycan attached covalently to a synthetic antigen provoking anti-phage antibodies. Immunology 1978;35:573-579.
    External Resources
  134. Arnon R, Sela M, Parant M, Chedid L: Antiviral response elicited by a completely synthetic antigen with built-in adjuvanticity. Proc Natl Acad Sci USA 1980;77:6769-6772.
  135. Steinbergs J, Kilchewska K, Lazdina U, Dishlers A, Ose V, Sällberg M, Tsimanis A: Short synthetic CDR-peptides forming the antibody combining site of the monoclonal antibody against RNA bacteriophage fr neutralize the phage activity. Hum Antibodies Hybridomas 1996;7:106-112.
    External Resources
  136. Liu JL, Zabetakis D, Goldman ER, Anderson GP: Selection and evaluation of single domain antibodies toward MS2 phage and coat protein. Mol Immunol 2013;53:118-125.
  137. Borisova G., Bundule M, Grinstein E, Dreilina D, Dreimane A, Kalis J, Kozlovskaya T, Loseva V, Ose V, Pumpen P, Pushko P, Snikere D, Stankevica E, Tsibinogin V, Gren EJ: Recombinant capsid structures for exposure of protein antigenic epitopes. Mol Gen (Life Sci Adv) 1987;6:169-174.
  138. Gren EJ, Pumpen P: Recombinant viral capsids as a new age of immunogenic proteins and vaccines (in Russian). J All Union Mendeleyevs Chem Soc 1988;33:531-536.
  139. Mastico RA, Talbot SJ, Stockley PG: Multiple presentation of foreign peptides on the surface of an RNA-free spherical bacteriophage capsid. J Gen Virol 1993;74:541-548.
  140. Kozlovskaia TM, Pushko PM, Stankevich EI, Dreimane AIa, Sniker DIa, Grinstein EE, Dreilinia DE, Veinia AE, Ose VP, Pumpen P, Gren EJ: Genetically engineered mutants of the envelope protein of the RNA-containing bacteriophage fr (in Russian). Mol Biol 1988;22:731-740.
    External Resources
  141. Pushko P, Kozlovskaya T, Sominskaya I, Brede A, Stankevica E, Ose V, Pumpens P, Grens E: Analysis of RNA phage fr coat protein assembly by insertion, deletion and substitution mutagenesis. Protein Eng 1993;6:883-891.
  142. Axblom C, Tars K, Fridborg K, Orna L, Bundule M, Liljas L: Structure of phage fr capsids with a deletion in the FG loop: implications for viral assembly. Virology 1998;249:80-88.
  143. Stonehouse NJ, Stockley PG: Effects of amino acid substitution on the thermal stability of MS2 capsids lacking genomic RNA. FEBS Lett 1993;334:355-359.
  144. Peabody DS: Subunit fusion confers tolerance to peptide insertions in a virus coat protein. Arch Biochem Biophys 1997;347:85-92.
  145. Heal KG, Hill HR, Stockley PG, Hollingdale MR, Taylor-Robinson AW: Expression and immunogenicity of a liver stage malaria epitope presented as a foreign peptide on the surface of RNA-free MS2 bacteriophage capsids. Vaccine 2000;18:251-258.
  146. Voronkova T, Grosch A, Kazaks A, Ose V, Skrastina D, Sasnauskas K, Jandrig B, Arnold W, Scherneck S, Pumpens P, Ulrich R: Chimeric bacteriophage fr virus-like particles harboring the immunodominant C-terminal region of hamster polyomavirus VP1 induce a strong VP1-specific antibody response in mice. Viral Immunol 2002;15:627-643.
  147. Pumpens P, Razanskas R, Pushko P, Renhof R, Gusars I, Skrastina D, Ose V, Borisova G, Sominskaya I, Petrovskis I, Jansons J, Sasnauskas K: Evaluation of HBs, HBc, and frCP virus-like particles for expression of human papillomavirus 16 E7 oncoprotein epitopes. Intervirology 2002;45:24-32.
  148. Kozlovska TM, Cielens I, Vasiljeva I, Strelnikova A, Kazaks A, Dislers A, Dreilina D, Ose V, Gusars I, Pumpens P: RNA phage Qβ coat protein as a carrier for foreign epitopes. Intervirology 1996;39:9-15.
    External Resources
  149. Kozlovska TM, Cielens I, Vasiljeva I, Bundule M, Strelnikova A, Kazaks A, Dislers A, Dreilina D, Ose V, Gusars I, Pumpens P: Display vectors. II. Recombinant capsid of RNA bacteriophage Qβ as a display moiety. Proc Latv Acad Sci 1997;51:8-12.
  150. Rumnieks J, Tars K: Crystal structure of the read-through domain from bacteriophage Qβ A1 protein. Protein Sci 2011;20:1707-1712.
  151. Smiley BK, Minion FC: Enhanced readthrough of opal (UGA) stop codons and production of Mycoplasma pneumoniae P1 epitopes in Escherichia coli. Gene 1993;134:33-40.
  152. Vasiljeva I, Kozlovska T, Cielens I, Strelnikova A, Kazaks A, Ose V, Pumpens P: Mosaic Qβ coats as a new presentation model. FEBS Lett 1998;431:7-11.
  153. Fehr T, Skrastina D, Pumpens P, Zinkernagel RM: T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant virus particles. Proc Natl Acad Sci USA 1998;95:9477-9481.
  154. Lim F, Spingola M, Peabody DS: The RNA-binding site of bacteriophage Qβ coat protein. J Biol Chem 1996;271:31839-31845.
  155. Spingola M, Peabody DS: MS2 coat protein mutants which bind Qβ RNA. Nucleic Acids Res 1997;25:2808-2815.
  156. Pickett GG, Peabody DS: Encapsidation of heterologous RNAs by bacteriophage MS2 coat protein. Nucleic Acids Res 1993;21:4621-4626.
  157. Cielens I, Ose V, Petrovskis I, Strelnikova A, Renhofa R, Kozlovska T, Pumpens P: Mutilation of RNA phage Qβ virus-like particles: from icosahedrons to rods. FEBS Lett 2000;482:261-264.
  158. van Meerten D, Olsthoorn RC, van Duin J, Verhaert RM: Peptide display on live MS2 phage: restrictions at the RNA genome level. J Gen Virol 2001;82:1797-1805.
  159. Peabody DS, Manifold-Wheeler B, Medford A, Jordan SK, do Carmo Caldeira J, Chackerian B: Immunogenic display of diverse peptides on virus-like particles of RNA phage MS2. J Mol Biol 2008;380:252-263.
  160. Chackerian B, Caldeira Jdo C, Peabody J, Peabody DS: Peptide epitope identification by affinity selection on bacteriophage MS2 virus-like particles. J Mol Biol 2011;409:225-237.
  161. Sominskaya I, Pushko P, Dreilina D, Kozlovskaya T, Pumpens P: Determination of the minimal length of preS1 epitope recognized by a monoclonal antibody which inhibits attachment of hepatitis B virus to hepatocytes. Med Microbiol Immunol 1992;181:215-226.
  162. Sominskaya I, Bichko V, Pushko P, Dreimane A, Snikere D, Pumpens P: Tetrapeptide QDPR is a minimal immunodominant epitope within the preS2 domain of hepatitis B virus. Immunol Lett 1992;33:169-172.
  163. Sällberg M, Pushko P, Berzinsh I, Bichko V, Sillekens P, Noah M, Pumpens P, Grens E, Wahren B, Magnius LO: Immunochemical structure of the carboxy-terminal part of hepatitis B e antigen: identification of internal and surface-exposed sequences. J Gen Virol 1993;74:1335-1340.
  164. Meisel H, Sominskaya I, Pumpens P, Pushko P, Borisova G, Deepen R, Lu X, Spiller GH, Kruger DH, Grens E, Gerlich WH: Fine-mapping and functional characterization of two immuno-dominant regions from the preS2 sequence of hepatitis B virus. Intervirology 1994;275:330-339.
    External Resources
  165. Sobotta D, Sominskaya I, Jansons J, Meisel H, Schmitt S, Heermann K-H, Kaluza G, Pumpens P, Gerlich WH: Mapping of immunodominant B-cell epitopes and the human serum albumin-binding site in natural hepatitis B virus surface antigen of defined genosubtype. J Gen Virol 2000;81:369-378.
  166. Sominskaya I, Paulij W, Jansons J, Sobotta D, Dreilina D, Sunnen C, Meisel H, Gerlich WH, Pumpens P: Fine-mapping of the B-cell epitope domain at the N-terminus of the preS2 region of the hepatitis B surface antigen. J Immunol Meth 2002;260:251-261.
  167. Jegerlehner A, Storni T, Lipowsky G, Schmid M, Pumpens P, Bachmann MF: Regulation of IgG antibody responses by epitope density and CD21-mediated costimulation. Eur J Immunol 2002;32:3305-3314.
  168. Jegerlehner A, Tissot A, Lechner F, Sebbel P, Erdmann I, Kündig T, Bächi T, Storni T, Jennings G, Pumpens P, Renner WA, Bachmann MF: A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses. Vaccine 2002;20:3104-3112.
  169. Bachmann MF, Dyer MR: Therapeutic vaccination for chronic diseases: a new class of drugs in sight. Nat Rev Drug Discov 2004;3:81-88.
  170. Dyer MR, Renner WA, Bachmann MF: A second vaccine revolution for the new epidemics of the 21st century. Drug Discov Today 2006;11:1028-1033.
  171. Bachmann MF, Jennings GT: Therapeutic vaccines for chronic diseases: successes and technical challenges. Philos Trans R Soc Lond B Biol Sci 2011;366:2815-2822.
  172. Peabody DS: A viral platform for chemical modification and multivalent display. J Nanobiotechnol 2003;1:5.
  173. Cheng YJ, Liang JX, Li QG: Construction of RNA-containing virus-like nanoparticles expression vector with cysteine residues on surface and fluorescent decoration (in Chinese). Yi Chuan Xue Bao 2005;32:874-878.
    External Resources
  174. Patel KG, Swartz JR: Surface functionalization of virus-like particles by direct conjugation using azide-alkyne click chemistry. Bioconjug Chem 2011;22:376-387.
  175. Hooker JM, Kovacs EW, Francis MB: Interior surface modification of bacteriophage MS2. J Am Chem Soc 2004;126:3718-3719.
  176. Cheng Y, Niu J, Zhang Y, Huang J, Li Q: Preparation of His-tagged armored RNA phage particles as a control for real-time reverse transcription-PCR detection of severe acute respiratory syndrome coronavirus. J Clin Microbiol 2006;44:3557-3561.
  177. Udit AK, Brown S, Baksh MM, Finn MG: Immobilization of bacteriophage Qβ on metal-derivatized surfaces via polyvalent display of hexahistidine tags. J Inorg Biochem 2008;102:2142-2146.
  178. Udit AK, Hollingsworth W, Choi K: Metal- and metallocycle-binding sites engineered into polyvalent virus-like scaffolds. Bioconjug Chem 2010;21:399-404.
  179. Strable E, Prasuhn DE Jr, Udit AK, Brown S, Link AJ, Ngo JT, Lander G, Quispe J, Potter CS, Carragher B, Tirrell DA, Finn MG: Unnatural amino acid incorporation into virus-like particles. Bioconjug Chem 2008;19:866-875.
  180. Smith MT, Varner CT, Bush DB, Bundy BC: The incorporation of the A2 protein to produce novel Qβ virus-like particles using cell-free protein synthesis. Biotechnol Prog 2012;28:549-555.
  181. Brune KD, Leneghan DB, Brian IJ, Ishizuka AS, Bachmann MF, Draper SJ, Biswas S, Howarth M: Plug-and-display: decoration of virus-like particles via isopeptide bonds for modular immunization. Sci Rep 2016;6:19234.
  182. Thrane S, Janitzek CM, Matondo S, Resende M, Gustavsson T, de Jongh WA, Clemmensen S, Roeffen W, van de Vegte-Bolmer M, van Gemert GJ, Sauerwein R, Schiller JT, Nielsen MA, Theander TG, Salanti A, Sander AF: Bacterial superglue enables easy development of efficient virus-like particle based vaccines. J Nanobiotechnol 2016;14:30.
  183. Zakeri B, Fierer JO, Celik E, Chittock EC, Schwarz-Linek U, Moy VT, Howarth M: Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin. Proc Natl Acad Sci USA 2012;109:E690-E697.
  184. Veggiani G, Zakeri B, Howarth M: Superglue from bacteria: unbreakable bridges for protein nanotechnology. Trends Biotechnol 2014;32:506-512.
  185. Peabody DS, Al-Bitar L: Isolation of viral coat protein mutants with altered assembly and aggregation properties. Nucleic Acids Res 2001;29:E113.
  186. Lima SM, Peabody DS, Silva JL, de Oliveira AC: Mutations in the hydrophobic core and in the protein-RNA interface affect the packing and stability of icosahedral viruses. Eur J Biochem 2004;271:135-145.
  187. Ashcroft AE, Lago H, Macedo JM, Horn WT, Stonehouse NJ, Stockley PG: Engineering thermal stability in RNA phage capsids via disulphide bonds. J Nanosci Nanotechnol 2005;5:2034-2041.
  188. Bundy BC, Swartz JR: Efficient disulfide bond formation in virus-like particles. J Biotechnol 2011;154:230-239.
  189. Fiedler JD, Higginson C, Hovlid ML, Kislukhin AA, Castillejos A, Manzenrieder F, Campbell MG, Voss NR, Potter CS, Carragher B, Finn MG: Engineered mutations change the structure and stability of a virus-like particle. Biomacromolecules 2012;13:2339-2348.
  190. Caldeira JC, Peabody DS: Thermal stability of RNA phage virus-like particles displaying foreign peptides. J Nanobiotechnol 2011;9:22.
  191. Caldeira Jdo C, Medford A, Kines RC, Lino CA, Schiller JT, Chackerian B, Peabody DS: Immunogenic display of diverse peptides, including a broadly cross-type neutralizing human papillomavirus L2 epitope, on virus-like particles of the RNA bacteriophage PP7. Vaccine 2010;28:4384-4393.
  192. Temizoz B, Kuroda E, Ishii KJ: Vaccine adjuvants as potential cancer immunotherapeutics. Int Immunol 2016;28:329-338.
  193. Brencicova E, Diebold SS: Nucleic acids and endosomal pattern recognition: how to tell friend from foe? Front Cell Infect Microbiol 2013;3:37.
  194. Jennings GT, Bachmann MF: Designing recombinant vaccines with viral properties: a rational approach to more effective vaccines. Curr Mol Med 2007;7:143-155.
  195. Chackerian B: Virus-like particles: flexible platforms for vaccine development. Expert Rev Vaccines 2007;6:381-390.
  196. Jennings GT, Bachmann MF: The coming of age of virus-like particle vaccines. Biol Chem 2008;389:521-536.
  197. Bachmann MF, Jennings GT: Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 2010;10:787-796.
  198. Pushko P, Pumpens P, Grens E: Development of virus-like particle technology from small highly symmetric to large complex virus-like particle structures. Intervirology 2013;56:141-165.
  199. Diederich S, Gedvilaite A, Zvirbliene A, Kazaks A, Sasnauskas K, Johnson N, Ulrich RG: Virus-like particles: a versatile tool for basic and applied research on emerging and reemerging viruses; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 137-160.
    External Resources
  200. Lundstrom K: Cancer therapy applying viral nanoparticles; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 455-466.
    External Resources
  201. Bachmann MF, Zabel F: Immunology of virus-like particles; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 121-128.
    External Resources
  202. Lee KL, Twyman RM, Fiering S, Steinmetz NF: Virus-based nanoparticles as platform technologies for modern vaccines. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016;8:554-578.
  203. Chackerian B, Peabody DS: Bacteriophage virus-like particles as a platform for vaccine discovery; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 239-250.
    External Resources
  204. Fu Y, Li J: A novel delivery platform based on bacteriophage MS2 virus-like particles. Virus Res 2016;211:9-16.
  205. Tumban E, Peabody J, Peabody DS, Chackerian B: A pan-HPV vaccine based on bacteriophage PP7 VLPs displaying broadly cross-neutralizing epitopes from the HPV minor capsid protein, L2. PLoS One 2011;6:e23310.
  206. Hunter Z, Tumban E, Dziduszko A, Chackerian B: Aerosol delivery of virus-like particles to the genital tract induces local and systemic antibody responses. Vaccine 2011;29:4584-4592.
  207. Tumban E, Peabody J, Peabody DS, Chackerian B: A universal virus-like particle-based vaccine for human papillomavirus: longevity of protection and role of endogenous and exogenous adjuvants. Vaccine 2013;31:4647-4654.
  208. Tyler M, Tumban E, Dziduszko A, Ozbun MA, Peabody DS, Chackerian B: Immunization with a consensus epitope from human papillomavirus L2 induces antibodies that are broadly neutralizing. Vaccine 2014;32:4267-4274.
  209. Tyler M, Tumban E, Peabody DS, Chackerian B: The use of hybrid virus-like particles to enhance the immunogenicity of a broadly protective HPV vaccine. Biotechnol Bioeng 2014;111:2398-2406.
  210. Tumban E, Muttil P, Escobar CA, Peabody J, Wafula D, Peabody DS, Chackerian B: Preclinical refinements of a broadly protective VLP-based HPV vaccine targeting the minor capsid protein, L2. Vaccine 2015;33:3346-3353.
  211. Tumban E, Peabody J, Tyler M, Peabody DS, Chackerian B: VLPs displaying a single L2 epitope induce broadly cross-neutralizing antibodies against human papillomavirus. PLoS One 2012;7:e49751.
  212. Jiang RT, Schellenbacher C, Chackerian B, Roden RB: Progress and prospects for L2-based human papillomavirus vaccines. Expert Rev Vaccines 2016;10:1-10.
  213. Ord RL, Caldeira JC, Rodriguez M, Noe A, Chackerian B, Peabody DS, Gutierrez G, Lobo CA: A malaria vaccine candidate based on an epitope of the Plasmodium falciparum RH5 protein. Malar J 2014;13:326.
  214. Crossey E, Frietze K, Narum DL, Peabody DS, Chackerian B: Identification of an immunogenic mimic of a conserved epitope on the Plasmodium falciparum blood stage antigen AMA1 using virus-like particle (VLP) peptide display. PLoS One 2015;10:e0132560.
  215. Cielens I, Jackevica L, Strods A, Kazaks A, Ose V, Bogans J, Pumpens P, Renhofa R: Mosaic RNA phage VLPs carrying domain III of the West Nile virus E protein. Mol Biotechnol 2014;56:459-469.
  216. Bachmann MF, Rohrer UH, Kündig TM, Bürki K, Hengartner H, Zinkernagel RM: The influence of antigen organization on B cell responsiveness. Science 1993;262:1448-1451.
  217. Senti G, Johansen P, Haug S, Bull C, Gottschaller C, Müller P, Pfister T, Maurer P, Bachmann MF, Graf N, Kündig TM: Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial. Clin Exp Allergy 2009;39:562-570.
  218. Klimek L, Willers J, Hammann-Haenni A, Pfaar O, Stocker H, Mueller P, Renner WA, Bachmann MF: Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study. Clin Exp Allergy 2011;41:1305-1312.
  219. Klimek L, Schendzielorz P, Mueller P, Saudan P, Willers J: Immunotherapy of allergic rhinitis: new therapeutic opportunities with virus-like particles filled with CpG motifs. Am J Rhinol Allergy 2013;27:206-212.
  220. Beeh KM, Kanniess F, Wagner F, Schilder C, Naudts I, Hammann-Haenni A, Willers J, Stocker H, Mueller P, Bachmann MF, Renner WA: The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma. J Allergy Clin Immunol 2013;131:866-874.
  221. Casale TB, Cole J, Beck E, Vogelmeier CF, Willers J, Lassen C, Hammann-Haenni A, Trokan L, Saudan P, Wechsler ME: CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled phase 2b study. Allergy 2015;70:1160-1168.
  222. Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann MF: Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J Immunol 2004;172:1777-1785.
  223. Bachmann MF, Schwarz K, Wolint P, Meijerink E, Martin S, Manolova V, Oxenius A: Cutting edge: distinct roles for T help and CD40/CD40 ligand in regulating differentiation of proliferation-competent memory CD8+ T cells. J Immunol 2004;173:2217-2221.
  224. Schwarz K, Meijerink E, Speiser DE, Tissot AC, Cielens I, Renhof R, Dishlers A, Pumpens P, Bachmann MF: Efficient homologous prime-boost strategies for T cell vaccination based on virus-like particles. Eur J Immunol 2005;35:816-821.
  225. Bachmann MF, Wolint P, Schwarz K, Jäger P, Oxenius A: Functional properties and lineage relationship of CD8+ T cell subsets identified by expression of IL-7 receptor α and CD62L. J Immunol 2005;175:4686-4696.
  226. Bessa J, Schmitz N, Hinton HJ, Schwarz K, Jegerlehner A, Bachmann MF: Efficient induction of mucosal and systemic immune responses by virus-like particles administered intranasally: implications for vaccine design. Eur J Immunol 2008;38:114-126.
  227. Agnellini P, Wiesel M, Schwarz K, Wolint P, Bachmann MF, Oxenius A: Kinetic and mechanistic requirements for helping CD8 T cells. J Immunol 2008;180:1517-1525.
  228. Keller SA, Bauer M, Manolova V, Muntwiler S, Saudan P, Bachmann MF: Cutting edge: limited specialization of dendritic cell subsets for MHC class II-associated presentation of viral particles. J Immunol 2010;184:26-29.
  229. Keller SA, Schwarz K, Manolova V, von Allmen CE, Kinzler MG, Bauer M, Muntwiler S, Saudan P, Bachmann MF: Innate signaling regulates cross-priming at the level of DC licensing and not antigen presentation. Eur J Immunol 2010;40:103-112.
  230. Jegerlehner A, Wiesel M, Dietmeier K, Zabel F, Gatto D, Saudan P, Bachmann MF: Carrier induced epitopic suppression of antibody responses induced by virus-like particles is a dynamic phenomenon caused by carrier-specific antibodies. Vaccine 2010;28:5503-5512.
  231. Maurer P, Jennings GT, Willers J, Rohner F, Lindman Y, Roubicek K, Renner WA, Müller P, Bachmann MF: A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity. Eur J Immunol 2005;35:2031-2040.
  232. Cornuz J, Zwahlen S, Jungi WF, Osterwalder J, Klingler K, van Melle G, Bangala Y, Guessous I, Müller P, Willers J, Maurer P, Bachmann MF, Cerny T: A vaccine against nicotine for smoking cessation: a randomized controlled trial. PLoS One 2008;3:e2547.
  233. Beerli RR, Bauer M, Buser RB, Gwerder M, Muntwiler S, Maurer P, Saudan P, Bachmann MF: Isolation of human monoclonal antibodies by mammalian cell display. Proc Natl Acad Sci USA 2008;105:14336-14341.
  234. Lang R, Winter G, Vogt L, Zurcher A, Dorigo B, Schimmele B: Rational design of a stable, freeze-dried virus-like particle-based vaccine formulation. Drug Dev Ind Pharm 2009;35:83-97.
  235. Yin Z, Comellas-Aragones M, Chowdhury S, Bentley P, Kaczanowska K, Benmohamed L, Gildersleeve JC, Finn MG, Huang X: Boosting immunity to small tumor-associated carbohydrates with bacteriophage Qβ capsids. ACS Chem Biol 2013;8:1253-1262.
  236. Yin Z, Dulaney S, McKay CS, Baniel C, Kaczanowska K, Ramadan S, Finn MG, Huang X: Chemical synthesis of GM2 glycans, bioconjugation with bacteriophage Qβ, and the induction of anticancer antibodies. Chembiochem 2016;17:174-180.
  237. Chackerian B, Frietze KM: Moving towards a new class of vaccines for non-infectious chronic diseases. Expert Rev Vaccines 2016;15:561-563.
  238. Klimek L, Willers J, Schendzielorz P, Kündig TM, Senti G: Immuntherapie der allergischen Rhinitis ohne Allergene? Neue Möglichkeiten einer Immunmodulation durch Vakzinierung mittels ‘virus-like particles' und CpG-Motiven. HNO 2013;61:826-833.
  239. Klimek L, Pfaar O: A comparison of immunotherapy delivery methods for allergen immunotherapy. Expert Rev Clin Immunol 2013;9:465-474, quiz 475.
  240. Klimek L, Bachmann MF, Senti G, Kündig TM: Immunotherapy of type-1 allergies with virus-like particles and CpG-motifs. Expert Rev Clin Immunol 2014;10:1059-1067.
  241. Fettelschoss A, Zabel F, Bachmann MF: Vaccination against Alzheimer disease: an update on future strategies. Hum Vaccin Immunother 2014;10:847-851.
  242. Gradman AH, Pinto R: Vaccination: a novel strategy for inhibiting the renin-angiotensin-aldosterone system. Curr Hypertens Rep 2008;10:473-479.
  243. Miller SA, Accardi JR, St Onge EL: Angiotensin II vaccine: a novel approach in the treatment of hypertension. Expert Opin Biol Ther 2008;8:1669-1673.
  244. Phisitkul S: CYT-006-AngQb, a vaccine against angiotensin II for the potential treatment of hypertension. Curr Opin Investig Drugs 2009;10:269-275.
    External Resources
  245. Sączyńska V: Influenza virus hemagglutinin as a vaccine antigen produced in bacteria. Acta Biochim Pol 2014;61:561-572.
    External Resources
  246. Pushko P, Tumpey TM: Traditional and novel trends in influenza vaccines; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 419-447.
    External Resources
  247. Reyes-Sandoval A, Bachmann MF: Plasmodium vivax malaria vaccines: why are we where we are? Hum Vaccin Immunother 2013;9:2558-2565.
  248. Heading CE: Drug evaluation: CYT-002-NicQb, a therapeutic vaccine for the treatment of nicotine addiction. Curr Opin Investig Drugs 2007;8:71-77.
    External Resources
  249. Maurer P, Bachmann MF: Vaccination against nicotine: an emerging therapy for tobacco dependence. Expert Opin Investig Drugs 2007;16:1775-1783.
  250. Raupach T, Hoogsteder PH, Onno van Schayck CP: Nicotine vaccines to assist with smoking cessation: current status of research. Drugs 2012;72:e1-16.
  251. Hartmann-Boyce J, Cahill K, Hatsukami D, Cornuz J: Nicotine vaccines for smoking cessation. Cochrane Database Syst Rev 2012;8:CD007072.
  252. Pentel PR, LeSage MG: New directions in nicotine vaccine design and use. Adv Pharmacol 2014;69:553-580.
  253. Koudelka KJ, Pitek AS, Manchester M, Steinmetz NF: Virus-based nanoparticles as versatile nanomachines. Annu Rev Virol 2015;2:379-401.
  254. Tsvetkova I, Dragnea B: Principles of design of virus nanoparticles for imaging applications; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 383-390.
    External Resources
  255. Karimi M, Mirshekari H, Moosavi Basri SM, Bahrami S, Moghoofei M, Hamblin MR: Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos. Adv Drug Deliv Rev 2016;106:45-62.
  256. Lee EJ, Lee NK, Kim IS: Bioengineered protein-based nanocage for drug delivery. Adv Drug Deliv Rev 2016;106:157-171.
  257. Wu M, Brown WL, Stockley PG: Cell-specific delivery of bacteriophage-encapsidated ricin A chain. Bioconjug Chem 1995;6:587-595.
  258. Wu M, Brown WL, Hill HR, Stockley PG: Specific cytotoxicity against cells bearing HIV1 gp120 antigen by bacteriophage-encapsidated ricin A chain: implications for cell specific drug delivery. Biochem Soc Trans 1997;25:158S.
  259. Wu M, Brown WL, Hill HR, Stockley PG: Development of a novel drug-delivery system using bacteriophage MS2 capsids. Biochem Soc Trans 1996;24:413S.
  260. Brown WL, Mastico RA, Wu M, Heal KG, Adams CJ, Murray JB, Simpson JC, Lord JM, Taylor-Robinson AW, Stockley PG: RNA bacteriophage capsid-mediated drug delivery and epitope presentation. Intervirology 2002;45:371-380.
  261. Yan R, Hallam A, Stockley PG, Boyes J: Oncogene dependency and the potential of targeted RNAi-based anti-cancer therapy. Biochem J 2014;461:1-13.
  262. Kovacs EW, Hooker JM, Romanini DW, Holder PG, Berry KE, Francis MB: Dual-surface-modified bacteriophage MS2 as an ideal scaffold for a viral capsid-based drug delivery system. Bioconjug Chem 2007;18:1140-1147.
  263. Carrico ZM, Romanini DW, Mehl RA, Francis MB: Oxidative coupling of peptides to a virus capsid containing unnatural amino acids. Chem Commun 2008;10:1205-1207.
  264. Wu W, Hsiao SC, Carrico ZM, Francis MB: Genome-free viral capsids as multivalent carriers for taxol delivery. Angew Chem Int Ed Engl 2009;48:9493-9497.
  265. Tong GJ, Hsiao SC, Carrico ZM, Francis MB: Viral capsid DNA aptamer conjugates as multivalent cell-targeting vehicles. J Am Chem Soc 2009;131:11174-11178.
  266. Stephanopoulos N, Carrico ZM, Francis MB: Nanoscale integration of sensitizing chromophores and porphyrins with bacteriophage MS2. Angew Chem Int Ed Engl 2009;48:9498-9502.
  267. Stephanopoulos N, Tong GJ, Hsiao SC, Francis MB: Dual-surface modified virus capsids for targeted delivery of photodynamic agents to cancer cells. ACS Nano 2010;4:6014-6020.
  268. Ashley CE, Carnes EC, Phillips GK, Durfee PN, Buley MD, Lino CA, Padilla DP, Phillips B, Carter MB, Willman CL, Brinker CJ, Caldeira Jdo C, Chackerian B, Wharton W, Peabody DS: Cell-specific delivery of diverse cargos by bacteriophage MS2 virus-like particles. ACS Nano 2011;5:5729-5745.
  269. Hou B, Saudan P, Ott G, Wheeler ML, Ji M, Kuzmich L, Lee LM, Coffman RL, Bachmann MF, DeFranco AL: Selective utilization of Toll-like receptor and MyD88 signaling in B cells for enhancement of the antiviral germinal center response. Immunity 2011;34:375-384.
  270. Link A, Zabel F, Schnetzler Y, Titz A, Brombacher F, Bachmann MF: Innate immunity mediates follicular transport of particulate but not soluble protein antigen. J Immunol 2012;188:3724-3733.
  271. Anderson EA, Isaacman S, Peabody DS, Wang EY, Canary JW, Kirshenbaum K: Viral nanoparticles donning a paramagnetic coat: conjugation of MRI contrast agents to the MS2 capsid. Nano Lett 2006;6:1160-1164.
  272. Hooker JM, Datta A, Botta M, Raymond KN, Francis MB: Magnetic resonance contrast agents from viral capsid shells: a comparison of exterior and interior cargo strategies. Nano Lett 2007;7:2207-2210.
  273. Hooker JM, O'Neil JP, Romanini DW, Taylor SE, Francis MB: Genome-free viral capsids as carriers for positron emission tomography radiolabels. Mol Imaging Biol 2008;10:182-191.
  274. Pasloske BL, Walkerpeach CR, Obermoeller RD, Winkler M, DuBois DB: Armored RNA technology for production of ribonuclease-resistant viral RNA controls and standards. J Clin Microbiol 1998;36:3590-3594.
    External Resources
  275. Zhang L, Sun Y, Chang L, Jia T, Wang G, Zhang R, Zhang K, Li J: A novel method to produce armored double-stranded DNA by encapsulation of MS2 viral capsids. Appl Microbiol Biotechnol 2015;99:7047-7057.
  276. Wei Y, Yang C, Wei B, Huang J, Wang L, Meng S, Zhang R, Li J: RNase-resistant virus-like particles containing long chimeric RNA sequences produced by two-plasmid coexpression system. J Clin Microbiol 2008;46:1734-1740.
  277. Ponchon L, Catala M, Seijo B, El Khouri M, Dardel F, Nonin-Lecomte S, Tisné C: Co-expression of RNA-protein complexes in Escherichia coli and applications to RNA biology. Nucleic Acids Res 2013;41:e150.
  278. Mikel P, Vasickova P, Kralik P: Methods for preparation of MS2 phage-like particles and their utilization as process control viruses in RT-PCR and qRT-PCR detection of RNA viruses from food matrices and clinical specimens. Food Environ Virol DOI 10.1007/s12560-015-9188-2. Published online: 25 February 2015.
  279. Frietze K, Peabody D, Chackerian B: Engineering virus-like particles as vaccine platforms. Curr Opin Virol 2016;18:44-49.
  280. Saboo S, Tumban E, Peabody J, Wafula D, Peabody DS, Chackerian B, Muttil P: An optimized formulation of a thermostable spray-dried virus-like particles vaccine against human papillomavirus. Mol Pharm 2016;13:1646-1655.
  281. Prel A, Caval V, Gayon R, Ravassard P, Duthoit C, Payen E, Maouche-Chretien L, Creneguy A, Nguyen TH, Martin N, Piver E, Sevrain R, Lamouroux L, Leboulch P, Deschaseaux F, Bouillé P, Sensébé L, Pagès JC: Highly efficient in vitro and in vivo delivery of functional RNAs using new versatile MS2-chimeric retrovirus-like particles. Mol Ther Methods Clin Dev 2015;2:15039.
  282. Frietze KM, Roden RB, Lee JH, Shi Y, Peabody DS, Chackerian B: Identification of anti-CA125 antibody responses in ovarian cancer patients by a novel deep sequence-coupled biopanning platform. Cancer Immunol Res 2016;4:157-164.
  283. Witus LS, Francis MB: Using synthetically modified proteins to make new materials. Acc Chem Res 2011;44:774-783.
  284. Stephanopoulos N, Liu M, Tong GJ, Li Z, Liu Y, Yan H, Francis MB: Immobilization and one-dimensional arrangement of virus capsids with nanoscale precision using DNA origami. Nano Lett 2010;10:2714-2720.
  285. Wang D, Capehart SL, Pal S, Liu M, Zhang L, Schuck PJ, Liu Y, Yan H, Francis MB, De Yoreo JJ: Hierarchical assembly of plasmonic nanostructures using virus capsid scaffolds on DNA origami templates. ACS Nano 2014;8:7896-7904.
  286. Friedman SD, Genthner FJ, Gentry J, Sobsey MD, Vinjé J: Gene mapping and phylogenetic analysis of the complete genome from 30 single-stranded RNA male-specific coliphages (family Leviviridae). J Virol 2009;83:11233-11243.
  287. Rumnieks J, Tars K: Diversity of pili-specific bacteriophages: genome sequence of IncM plasmid-dependent RNA phage M. BMC Microbiol 2012;12:277.
  288. Kannoly S, Shao Y, Wang IN: Rethinking the evolution of single-stranded RNA (ssRNA) bacteriophages based on genomic sequences and characterizations of two R-plasmid-dependent ssRNA phages, C-1 and Hgal1. J Bacteriol 2012;194:5073-5079.
  289. Friedman SD, Snellgrove WC, Genthner FJ: Genomic sequences of two novel levivirus single-stranded RNA coliphages (family Leviviridae): evidence for recombination in environmental strains. Viruses 2012;4:1548-1568.
  290. Vinjé J, Oudejans SJ, Stewart JR, Sobsey MD, Long SC: Molecular detection and genotyping of male-specific coliphages by reverse transcription-PCR and reverse line blot hybridization. Appl Environ Microbiol 2004;70:5996-6004.
  291. Greninger AL, DeRisi JL: Draft genome sequences of Leviviridae RNA phages EC and MB recovered from San Francisco wastewater. Genome Announc 2015;3:e00652-15.
  292. Krishnamurthy SR, Janowski AB, Zhao G, Barouch D, Wang D: Hyperexpansion of RNA bacteriophage diversity. PLoS Biol 2016;14:e1002409.
  293. Dykeman EC, Stockley PG, Twarock R: Solving a Levinthal's paradox for virus assembly identifies a unique antiviral strategy. Proc Natl Acad Sci USA 2014;111:5361-5366.
  294. Dika C, Duval JF, Ly-Chatain HM, Merlin C, Gantzer C: Impact of internal RNA on aggregation and electrokinetics of viruses: comparison between MS2 phage and corresponding virus-like particles. Appl Environ Microbiol 2011;77:4939-4948.
  295. Schmitz N, Beerli RR, Bauer M, Jegerlehner A, Dietmeier K, Maudrich M, Pumpens P, Saudan P, Bachmann MF: Universal vaccine against influenza virus: Linking TLR signaling to anti-viral protection. Eur J Immunol 2012;42:863-869.
  296. Crossey E, Amar MJ, Sampson M, Peabody J, Schiller JT, Chackerian B, Remaley AT: A cholesterol-lowering VLP vaccine that targets PCSK9. Vaccine 2015;33:5747-5755.
  297. Dong YM, Zhang GG, Huang XJ, Chen L, Chen HT: Promising MS2 mediated virus-like particle vaccine against foot-and-mouth disease. Antiviral Res 2015;117:39-43.
  298. Stockley PG, Mastico RA: Use of fusions to viral coat proteins as antigenic carriers for vaccine development. Methods Enzymol 2000;326:551-569.
  299. Lagoutte P, Mignon C, Donnat S, Stadthagen G, Mast J, Sodoyer R, Lugari A, Werle B: Scalable chromatography-based purification of virus-like particle carrier for epitope based influenza A vaccine produced in Escherichia coli. J Virol Methods 2016;232:8-11.
  300. Caldeira J, Bustos J, Peabody J, Chackerian B, Peabody DS: Epitope-specific anti-hCG vaccines on a virus like particle platform. PLoS One 2015;10:e0141407.
  301. Pastori C, Tudor D, Diomede L, Drillet AS, Jegerlehner A, Röhn TA, Bomsel M, Lopalco L: Virus like particle based strategy to elicit HIV-protective antibodies to the alpha-helic regions of gp41. Virology 2012;431:1-11.
  302. Freer G, Giannecchini S, Tissot A, Bachmann MF, Rovero P, Serres PF, Bendinelli M: Dissection of seroreactivity against the tryptophan-rich motif of the feline immunodeficiency virus transmembrane glycoprotein. Virology 2004;322:360-369.
  303. Huber A, Bachmann M, Jennings G, Tissot A, Langedijk J, Timmerman P, Slootstra J, Boshuizen R: Circular CCR5 peptide conjugates and uses thereof. WIPO Patent Application WO/2008/074895. June 26, 2008.
  304. Sommerfelt MA: Circular CCR5 peptide conjugates and uses thereof (WO2008074895). Expert Opin Ther Pat 2009;19:1323-1328.
  305. Hunter Z, Smyth HD, Durfee P, Chackerian B: Induction of mucosal and systemic antibody responses against the HIV coreceptor CCR5 upon intramuscular immunization and aerosol delivery of a virus-like particle based vaccine. Vaccine 2009;28:403-414.
  306. van Rompay KK, Hunter Z, Jayashankar K, Peabody J, Montefiori D, Labranche CC, Keele BF, Jensen K, Abel K, Chackerian B: A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge with simian immunodeficiency virus SIVmac251. J Virol 2014;88:2011-2024.
  307. Kündig TM, Senti G, Schnetzler G, Wolf C, Prinz Vavricka BM, Fulurija A, Hennecke F, Sladko K, Jennings GT, Bachmann MF: Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults. J Allergy Clin Immunol 2006;117:1470-1476.
  308. Schmitz N, Dietmeier K, Bauer M, Maudrich M, Utzinger S, Muntwiler S, Saudan P, Bachmann MF: Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy. J Exp Med 2009;206:1941-1955.
  309. Akache B, Weeratna RD, Deora A, Thorn JM, Champion B, Merson JR, Davis HL, McCluskie MJ: Anti-IgE Qβ-VLP conjugate vaccine self-adjuvants through activation of TLR7. Vaccines (Basel) 2016;4:3.
  310. Araujo RN, Franco PF, Rodrigues H, Santos LC, McKay CS, Sanhueza CA, Brito CR, Azevedo MA, Venuto AP, Cowan PJ, Almeida IC, Finn MG, Marques AF: Amblyomma sculptum tick saliva: α-Gal identification, antibody response and possible association with red meat allergy in Brazil. Int J Parasitol 2016;46:213-220.
  311. Chackerian B, Rangel M, Hunter Z, Peabody DS: Virus and virus-like particle-based immunogens for Alzheimer's disease induce antibody responses against amyloid-β without concomitant T cell responses. Vaccine 2006;24:6321-6331.
  312. Li QY, Gordon MN, Chackerian B, Alamed J, Ugen KE, Morgan D: Virus-like peptide vaccines against Aβ N-terminal or C-terminal domains reduce amyloid deposition in APP transgenic mice without addition of adjuvant. J Neuroimmune Pharmacol 2010;5:133-142.
  313. Wiessner C, Wiederhold KH, Tissot AC, Frey P, Danner S, Jacobson LH, Jennings GT, Lüönd R, Ortmann R, Reichwald J, Zurini M, Mir A, Bachmann MF, Staufenbiel M: The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. J Neurosci 2011;31:9323-9331.
  314. Tissot AC, Spohn G, Jennings GT, Shamshiev A, Kurrer MO, Windak R, Meier M, Viesti M, Hersberger M, Kündig TM, Ricci R, Bachmann MF: A VLP-based vaccine against interleukin-1α protects mice from atherosclerosis. Eur J Immunol 2013;43:716-722.
  315. Spohn G, Keller I, Beck M, Grest P, Jennings GT, Bachmann MF: Active immunization with IL-1 displayed on virus-like particles protects from autoimmune arthritis. Eur J Immunol 2008;38:877-887.
  316. Guler R, Parihar SP, Spohn G, Johansen P, Brombacher F, Bachmann MF: Blocking IL-1α but not IL-1β increases susceptibility to chronic Mycobacterium tuberculosis infection in mice. Vaccine 2011;29:1339-1346.
  317. Röhn TA, Jennings GT, Hernandez M, Grest P, Beck M, Zou Y, Kopf M, Bachmann MF: Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis. Eur J Immunol 2006;36:2857-2867.
  318. Sonderegger I, Röhn TA, Kurrer MO, Iezzi G, Zou Y, Kastelein RA, Bachmann MF, Kopf M: Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis. Eur J Immunol 2006;36:2849-2856.
  319. Dallenbach K, Maurer P, Röhn T, Zabel F, Kopf M, Bachmann MF: Protective effect of a germline, IL-17-neutralizing antibody in murine models of autoimmune inflammatory disease. Eur J Immunol 2015;45:1238-1247.
  320. Spohn G, Guler R, Johansen P, Keller I, Jacobs M, Beck M, Rohner F, Bauer M, Dietmeier K, Kündig TM, Jennings GT, Brombacher F, Bachmann MF: A virus-like particle-based vaccine selectively targeting soluble TNF-α protects from arthritis without inducing reactivation of latent tuberculosis. J Immunol 2007;178:7450-7457.
  321. Spohn G, Schori C, Keller I, Sladko K, Sina C, Guler R, Schwarz K, Johansen P, Jennings GT, Bachmann MF: Preclinical efficacy and safety of an anti-IL-1β vaccine for the treatment of type 2 diabetes. Mol Ther Methods Clin Dev 2014;1:14048.
  322. Cavelti-Weder C, Timper K, Seelig E, Keller C, Osranek M, Lässing U, Spohn G, Maurer P, Müller P, Jennings GT, Willers J, Saudan P, Donath MY, Bachmann MF: Development of an interleukin-1β vaccine in patients with type 2 diabetes. Mol Ther 2016;24:1003-1012.
  323. Zou Y, Sonderegger I, Lipowsky G, Jennings GT, Schmitz N, Landi M, Kopf M, Bachmann MF: Combined vaccination against IL-5 and eotaxin blocks eosinophilia in mice. Vaccine 2010;28:3192-3200.
  324. Chackerian B, Durfee MR, Schiller JT: Virus-like display of a neo-self antigen reverses B cell anergy in a B cell receptor transgenic mouse model. J Immunol 2008;180:5816-5825.
  325. Ambühl PM, Tissot AC, Fulurija A, Maurer P, Nussberger J, Sabat R, Nief V, Schellekens C, Sladko K, Roubicek K, Pfister T, Rettenbacher M, Volk HD, Wagner F, Müller P, Jennings GT, Bachmann MF: A vaccine for hypertension based on virus-like particles: preclinical efficacy and phase I safety and immunogenicity. J Hypertens 2007;25:63-72.
  326. Tissot AC, Maurer P, Nussberger J, Sabat R, Pfister T, Ignatenko S, Volk HD, Stocker H, Müller P, Jennings GT, Wagner F, Bachmann MF: Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. Lancet 2008;371:821-827.
  327. Chen X, Qiu Z, Yang S, Ding D, Chen F, Zhou Y, Wang M, Lin J, Yu X, Zhou Z, Liao Y: Effectiveness and safety of a therapeutic vaccine against angiotensin II receptor type 1 in hypertensive animals. Hypertension 2013;61:408-416.
  328. Ding D, Du Y, Qiu Z, Yan S, Chen F, Wang M, Yang S, Zhou Y, Hu X, Deng Y, Wang S, Wang L, Zhang H, Wu H, Yu X, Zhou Z, Liao Y, Chen X: Vaccination against type 1 angiotensin receptor prevents streptozotocin-induced diabetic nephropathy. J Mol Med 2016;94:207-218.
  329. Zhou Y, Wang S, Qiu Z, Song X, Pan Y, Hu X, Zhang H, Deng Y, Ding D, Wu H, Yang S, Wang M, Zhou Z, Liao Y, Chen X: ATRQβ-001 vaccine prevents atherosclerosis in apolipoprotein E-null mice. J Hypertens 2016;34:474-485.
  330. Röhn TA, Ralvenius WT, Paul J, Borter P, Hernandez M, Witschi R, Grest P, Zeilhofer HU, Bachmann MF, Jennings GT: A virus-like particle-based anti-nerve growth factor vaccine reduces inflammatory hyperalgesia: potential long-term therapy for chronic pain. J Immunol 2011;186:1769-1780.
  331. Skibinski DA, Hanson BJ, Lin Y, von Messling V, Jegerlehner A, Tee JB, Chye de H, Wong SK, Ng AA, Lee HY, Au B, Lee BT, Santoso L, Poidinger M, Fairhurst AM, Matter A, Bachmann MF, Saudan P, Connolly JE: Enhanced neutralizing antibody titers and Th1 polarization from a novel Escherichia coli derived pandemic influenza vaccine. PLoS One 2013;8:e76571.
  332. Jegerlehner A, Zabel F, Langer A, Dietmeier K, Jennings GT, Saudan P, Bachmann MF: Bacterially produced recombinant influenza vaccines based on virus-like particles. PLoS One 2013;8:e78947.
  333. Low JG, Lee LS, Ooi EE, Ethirajulu K, Yeo P, Matter A, Connolly JE, Skibinski DA, Saudan P, Bachmann M, Hanson BJ, Lu Q, Maurer-Stroh S, Lim S, Novotny-Diermayr V: Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine: results from a double-blinded, randomized phase I clinical trial in healthy Asian volunteers. Vaccine 2014;32:5041-5048.
  334. Khan F, Porter M, Schwenk R, DeBot M, Saudan P, Dutta S: Head-to-head comparison of soluble vs. Qβ VLP circumsporozoite protein vaccines reveals selective enhancement of NANP repeat responses. PLoS One 2015;10:e0142035.
  335. Speiser DE, Schwarz K, Baumgaertner P, Manolova V, Devevre E, Sterry W, Walden P, Zippelius A, Conzett KB, Senti G, Voelter V, Cerottini JP, Guggisberg D, Willers J, Geldhof C, Romero P, Kündig T, Knuth A, Dummer R, Trefzer U, Bachmann MF: Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients. J Immunother 2010;33:848-858.
  336. Braun M, Jandus C, Maurer P, Hammann-Haenni A, Schwarz K, Bachmann MF, Speiser DE, Romero P: Virus-like particles induce robust human T-helper cell responses. Eur J Immunol 2012;42:330-340.
  337. Goldinger SM, Dummer R, Baumgaertner P, Mihic-Probst D, Schwarz K, Hammann-Haenni A, Willers J, Geldhof C, Prior JO, Kündig TM, Michielin O, Bachmann MF, Speiser DE: Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8-T-cell responses in melanoma patients. Eur J Immunol 2012;42:3049-3061.
  338. McCluskie MJ, Thorn J, Gervais DP, Stead DR, Zhang N, Benoit M, Cartier J, Kim IJ, Bhattacharya K, Finneman JI, Merson JR, Davis HL: Anti-nicotine vaccines: comparison of adjuvanted CRM197 and Qβ-VLP conjugate formulations for immunogenicity and function in non-human primates. Int Immunopharmacol 2015;29:663-671.
  339. Fulurija A, Lutz TA, Sladko K, Osto M, Wielinga PY, Bachmann MF, Saudan P: Vaccination against GIP for the treatment of obesity. PLoS One 2008;3:e3163.
  340. Spohn G, Schwarz K, Maurer P, Illges H, Rajasekaran N, Choi Y, Jennings GT, Bachmann MF: Protection against osteoporosis by active immunization with TRANCE/RANKL displayed on virus-like particles. J Immunol 2005;175:6211-6218.
  341. Kalniņš G, Cielēns I, Renhofa R: Virus-like particles addressed by HBV preS1 sequences. Environ Exp Biol 2013;11:1-8.
  342. Rūmnieks J, Freivalds J, Cielēns I, Renhofa R: Specificity of packaging mRNAs in bacteriophage GA virus-like particles in yeast Saccharomyces cerevisiae. Acta Universitatis Latviensis Biol 2008;745:145-154.
  343. Strods A, Ārgule D, Cielēns I, Jackeviča L, Renhofa R: Expression of GA coat protein-derived mosaic virus-like particles in Saccharomyces cerevisiae and packaging in vivo of mRNAs into particles. Proc Latv Acad Sci 2012;66:234-241.
    External Resources
  344. Ārgule D, Cielēns I, Renhofa R, Strods A: In vivo packaging of yeast-produced bacteriophage GA derived virus-like particles. Proc Latv Acad Sci 2016, in press.
  345. Wu M, Sherwin T, Brown WL, Stockley PG: Delivery of antisense oligonucleotides to leukemia cells by RNA bacteriophage capsids. Nanomedicine 2005;1:67-76.
  346. Wei B, Wei Y, Zhang K, Wang J, Xu R, Zhan S, Lin G, Wang W, Liu M, Wang L, Zhang R, Li J: Development of an antisense RNA delivery system using conjugates of the MS2 bacteriophage capsids and HIV-1 TAT cell-penetrating peptide. Biomed Pharmacother 2009;63:313-318.
  347. Pan Y, Zhang Y, Jia T, Zhang K, Li J, Wang L: Development of a microRNA delivery system based on bacteriophage MS2 virus-like particles. FEBS J 2012;279:1198-1208.
  348. Pan Y, Jia T, Zhang Y, Zhang K, Zhang R, Li J, Wang L: MS2 VLP-based delivery of microRNA-146a inhibits autoantibody production in lupus-prone mice. Int J Nanomedicine 2012;7:5957-5967.
  349. Yao Y, Jia T, Pan Y, Gou H, Li Y, Sun Y, Zhang R, Zhang K, Lin G, Xie J, Li J, Wang L: Using a novel microRNA delivery system to inhibit osteoclastogenesis. Int J Mol Sci 2015;16:8337-8350.
  350. Galaway FA, Stockley PG: MS2 viruslike particles: a robust, semisynthetic targeted drug delivery platform. Mol Pharm 2013;10:59-68.
  351. Capehart SL, Coyle MP, Glasgow JE, Francis MB: Controlled integration of gold nanoparticles and organic fluorophores using synthetically modified MS2 viral capsids. J Am Chem Soc 2013;135:3011-3016.
  352. Cohen BA, Bergkvist M: Targeted in vitro photodynamic therapy via aptamer-labeled, porphyrin-loaded virus capsids. J Photochem Photobiol B 2013;121:67-74.
  353. ElSohly AM, Netirojjanakul C, Aanei IL, Jager A, Bendall SC, Farkas ME, Nolan GP, Francis MB: Synthetically modified viral capsids as versatile carriers for use in antibody-based cell targeting. Bioconjug Chem 2015;26:1590-1596.
  354. Chang L, Wang G, Jia T, Zhang L, Li Y, Han Y, Zhang K, Lin G, Zhang R, Li J, Wang L: Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma. Oncotarget 2016;7:23988-24004.
  355. Sun S, Li W, Sun Y, Pan Y, Li J: A new RNA vaccine platform based on MS2 virus-like particles produced in Saccharomyces cerevisiae. Biochem Biophys Res Commun 2011;407:124-128.
  356. Glasgow JE, Capehart SL, Francis MB, Tullman-Ercek D: Osmolyte-mediated encapsulation of proteins inside MS2 viral capsids. ACS Nano 2012;6:8658-8664.
  357. Li J, Sun Y, Jia T, Zhang R, Zhang K, Wang L: Messenger RNA vaccine based on recombinant MS2 virus-like particles against prostate cancer. Int J Cancer 2014;134:1683-1694.
  358. Steinmetz NF, Hong V, Spoerke ED, Lu P, Breitenkamp K, Finn MG, Manchester M: Buckyballs meet viral nanoparticles: candidates for biomedicine. J Am Chem Soc 2009;131:17093-17095.
  359. Rhee JK, Hovlid M, Fiedler JD, Brown SD, Manzenrieder F, Kitagishi H, Nycholat C, Paulson JC, Finn MG: Colorful virus-like particles: fluorescent protein packaging by the Qβ capsid. Biomacromolecules 2011;12:3977-3981.
  360. Rhee JK, Baksh M, Nycholat C, Paulson JC, Kitagishi H, Finn MG: Glycan-targeted virus-like nanoparticles for photodynamic therapy. Biomacromolecules 2012;13:2333-2338.
  361. Lau JL, Baksh MM, Fiedler JD, Brown SD, Kussrow A, Bornhop DJ, Ordoukhanian P, Finn MG: Evolution and protein packaging of small-molecule RNA aptamers. ACS Nano 2011;5:7722-7729.
  362. Wu Z, Tang LJ, Zhang XB, Jiang JH, Tan W: Aptamer-modified nanodrug delivery systems. ACS Nano 2011;5:7696-7699.
  363. Hovlid ML, Lau JL, Breitenkamp K, Higginson CJ, Laufer B, Manchester M, Finn MG: Encapsidated atom-transfer radical polymerization in Qβ virus-like nanoparticles. ACS Nano 2014;8:8003-8014.
  364. Fiedler JD, Brown SD, Lau JL, Finn MG: RNA-directed packaging of enzymes within virus-like particles. Angew Chem Int Ed Engl 2010;49:9648-9651.
  365. Hong V, Udit AK, Evans RA, Finn MG: Electrochemically protected copper(I)-catalyzed azide-alkyne cycloaddition. Chembiochem 2008;9:1481-1486.
  366. Kaltgrad E, O'Reilly MK, Liao L, Han S, Paulson JC, Finn MG: On-virus construction of polyvalent glycan ligands for cell-surface receptors. J Am Chem Soc 2008;130:4578-4579.
  367. Kussrow A, Kaltgrad E, Wolfenden ML, Cloninger MJ, Finn MG, Bornhop DJ: Measurement of monovalent and polyvalent carbohydrate-lectin binding by back-scattering interferometry. Anal Chem 2009;81:4889-4897.
  368. Udit AK, Everett C, Gale AJ, Reiber Kyle J, Ozkan M, Finn MG: Heparin antagonism by polyvalent display of cationic motifs on virus-like particles. Chembiochem 2009;10:503-510.
  369. Gale AJ, Elias DJ, Averell PM, Teirstein PS, Buck M, Brown SD, Polonskaya Z, Udit AK, Finn MG: Engineered virus-like nanoparticles reverse heparin anticoagulation more consistently than protamine in plasma from heparin-treated patients. Thromb Res 2011;128:e9-13.
  370. Udit AK: Engineered virus-like nanoparticle heparin antagonists. Conf Proc IEEE Eng Med Biol Soc 2013;2013:4118-4120.
  371. Brown SD, Fiedler JD, Finn MG: Assembly of hybrid bacteriophage Qβ virus-like particles. Biochemistry 2009;48:11155-11157.
  372. Astronomo RD, Kaltgrad E, Udit AK, Wang SK, Doores KJ, Huang CY, Pantophlet R, Paulson JC, Wong CH, Finn MG, Burton DR: Defining criteria for oligomannose immunogens for HIV using icosahedral virus capsid scaffolds. Chem Biol 2010;17:357-370.
  373. Banerjee D, Liu AP, Voss NR, Schmid SL, Finn MG: Multivalent display and receptor-mediated endocytosis of transferrin on virus-like particles. Chembiochem 2010;11:1273-1279.
  374. Cigler P, Lytton-Jean AK, Anderson DG, Finn MG, Park SY: DNA-controlled assembly of a NaTl lattice structure from gold nanoparticles and protein nanoparticles. Nat Mater 2010;9:918-922.
  375. Manzenrieder F, Luxenhofer R, Retzlaff M, Jordan R, Finn MG: Stabilization of virus-like particles with poly(2-oxazoline)s. Angew Chem Int Ed Engl 2011;50:2601-2605.
  376. Pokorski JK, Breitenkamp K, Liepold LO, Qazi S, Finn MG: Functional virus-based polymer-protein nanoparticles by atom transfer radical polymerization. J Am Chem Soc 2011;133:9242-9245.
  377. Pokorski JK, Hovlid ML, Finn MG: Cell targeting with hybrid Qβ virus-like particles displaying epidermal growth factor. Chembiochem 2011;12:2441-2447.
  378. Mead G, Hiley M, Ng T, Fihn C, Hong K, Groner M, Miner W, Drugan D, Hollingsworth W, Udit AK: Directed polyvalent display of sulfated ligands on virus nanoparticles elicits heparin-like anticoagulant activity. Bioconjug Chem 2014;25:1444-1452.
  379. Groner M, Ng T, Wang W, Udit AK: Bio-layer interferometry of a multivalent sulfated virus nanoparticle with heparin-like anticoagulant activity. Anal Bioanal Chem 2015;407:5843-5847.
  380. Isarov SA, Lee PW, Pokorski JK: ‘Graft-to' protein/polymer conjugates using polynorbornene block copolymers. Biomacromolecules 2016;17:641-648.
  381. Kang JS, Yoon JH: Dynamics of RNA bacteriophage MS2 observed with a long-lifetime metal-ligand complex. J Photosci 2004;11:35-40.
  382. Datta A, Hooker JM, Botta M, Francis MB, Aime S, Raymond KN: High relaxivity gadolinium hydroxypyridonate-viral capsid conjugates: nanosized MRI contrast agents. J Am Chem Soc 2008;130:2546-2552.
  383. Meldrum T, Seim KL, Bajaj VS, Palaniappan KK, Wu W, Francis MB, Wemmer DE, Pines A: A xenon-based molecular sensor assembled on an MS2 viral capsid scaffold. J Am Chem Soc 2010;132:5936-5937.
  384. Farkas ME, Aanei IL, Behrens CR, Tong GJ, Murphy ST, O'Neil JP, Francis MB: PET imaging and biodistribution of chemically modified bacteriophage MS2. Mol Pharm 2013;10:69-76.
  385. Obermeyer AC, Capehart SL, Jarman JB, Francis MB: Multivalent viral capsids with internal cargo for fibrin imaging. PLoS One 2014;9:e100678.
  386. Elena CM, Leticia F, Emilia T, Patricia E, Mariella T: Evaluation of a labelled bacteriophage with 99mTc as a potential agent for infection diagnosis. Curr Radiopharm 2016;9:137-142.
  387. Prasuhn DE Jr, Singh P, Strable E, Brown S, Manchester M, Finn MG: Plasma clearance of bacteriophage Qβ particles as a function of surface charge. J Am Chem Soc 2008;130:1328-1334.
  388. Kim MS, Kim JH, Son BW, Kang JS: Dynamics of bacteriophage R17 probed with a long-lifetime Ru(II) metal-ligand complex. J Fluoresc 2010;20:713-718.
  389. Carrillo-Tripp M, Shepherd CM, Borelli IA, Venkataraman S, Lander G, Natarajan P, Johnson JE, Brooks CL 3rd, Reddy VS: VIPERdb2: an enhanced and web API enabled relational database for structural virology. Nucleic Acids Res 2009;37:D436-D442.
  390. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE: UCSF Chimera - a visualization system for exploratory research and analysis. J Comput Chem 2004;25:1605-1612.

Author Contacts

Paul Pumpens

Baznicas 27/29-22

LV-1010 Riga (Latvia)

E-Mail paul@biomed.lu.lv


Article / Publication Details

First-Page Preview
Abstract of Review

Received: May 25, 2016
Accepted: August 30, 2016
Published online: November 10, 2016
Issue release date: December 2016

Number of Print Pages: 37
Number of Figures: 6
Number of Tables: 4

ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Loeb T, Zinder ND: A bacteriophage containing RNA. Proc Natl Acad Sci USA 1961;47:282-289.
  2. Davis J, Strauss J, Sinsheimer R: Bacteriophage MS2: another RNA phage. Science 1961;134:1427.
  3. Paranchych W, Graham AF: Isolation and properties of an RNA-containing bacteriophage. J Cell Comp Physiol 1962;60:199-208.
  4. Marvin DA, Hoffmann-Berling H: Physical and chemical properties of 2 new small bacteriophages. Nature 1963;197:517-518.
    External Resources
  5. Hofschneider PH: Untersuchungen über ‘kleine' E. coli K12 Bacteriophagen. I. Mitt.: Die Isolierung und einige Eigenschaften der ‘kleinen' Bacteriophagen M12, M13 und M20. Z Naturforsch 1963;18b:203-205.
    External Resources
  6. Watanabe I: Persistent infection with an RNA bacteriophage. Nippon Rinsho 1964;22:243-251.
  7. Gren EJ: Regulatory Mechanisms of RNA Bacteriophage Replication (in Russian). Riga, Zinatne, 1974.
  8. Zinder ND (ed): RNA Phages. Cold Spring Harbor, Cold Spring Harbor Laboratory, 1975.
  9. Zinder ND: Portraits of viruses: RNA phage. Intervirology 1980;13:257-270.
  10. Miyake T, Shiba T, Sakurai T, Watanabe I: Isolation and properties of two new RNA phages SP and FI. Jpn J Microbiol 1969;13:375-382.
  11. Aoi T, Furuse K, Watanabe I, Osawa S: Isolation and properties of temperature-sensitive mutants of group II RNA phage GA (in Japanese). Uirusu 1973;23:19-28.
  12. Schmidt JM, Stanier RY: Isolation and characterization of bacteriophages active against stalked bacteria. J Gen Microbiol 1965;39:95-107.
  13. Bradley D: The structure and infective process of a Pseudomonas aeruginosa bacteriophage containing ribonucleic acid. J Gen Microbiol 1966;45:83-96.
  14. Olsen RH, Thomas DD: Characteristics and purification of PRR1, an RNA phage specific for the broad host range Pseudomonas R1822 drug resistance plasmid. J Virol 1973;12:1560-1567.
    External Resources
  15. Coffi H: Lysotypie des Acinetobacter; MSc thesis, Laval University, Quebec, 1995.
  16. Klovins J, Overbeek GP, van den Worm SH, Ackermann HW, van Duin J: Nucleotide sequence of a ssRNA phage from Acinetobacter: kinship to coliphages. J Gen Virol 2002;83:1523-1533.
  17. International Committee on Taxonomy of Viruses: Virus Taxonomy: 2014 Release. EC 46, Montreal, Canada, July 2014. http://ictvonline.org/virusTaxonomy.asp.
  18. Inokuchi Y, Hirashima A. Watanabe I: Comparison of the nucleotide sequences at the 3′-terminal region of RNAs from RNA coliphages. J Mol Biol 1982;158:711-730.
  19. NCBI: Taxonomy browser. http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11989.
  20. Krueger RG: Serological relatedness of the ribonucleic acid-containing coliphages. J Virol 1969;4:567-573.
    External Resources
  21. Furuse K: Distribution of coliphages in the environment: general considerations; in Goyal SM, Gerba CP, Bitton G (eds): Phage Ecology. New York, John Wiley, 1987, pp 87-124.
  22. Miyake T, Haruna I, Shiba T, Ito YH, Yamane K: Grouping of RNA phages based on the template specificity of their RNA replicases. Proc Natl Acad Sci USA 1971;68:2022-2024.
  23. Hsu FC, Shieh YS, van Duin J, Beekwilder MJ, Sobsey MD: Genotyping male-specific RNA coliphages by hybridization with oligonucleotide probes. Appl Environ Microbiol 1995;61:3960-3966.
    External Resources
  24. Friedman SD, Cooper EM, Calci KR, Genthner FJ: Design and assessment of a real time reverse transcription-PCR method to genotype single-stranded RNA male-specific coliphages (family Leviviridae). J Virol Methods 2011;173:196-202.
  25. Guan D, Joerger RD, Kniel KE, Calci KR, Hicks DT, Pivarnik LF, Hoover DG: Effect of high hydrostatic pressure on four genotypes of F-specific RNA bacteriophages. J Appl Microbiol 2007;102:51-56.
  26. Muniesa M, Payan A, Moce-Llivina L, Blanch AR, Jofre J: Differential persistence of F-specific RNA phage subgroups hinders their use as single tracers for faecal source tracking in surface water. Water Res 2009;43:1559-1564.
  27. Hartard C, Rivet R, Banas S, Gantzer C: Occurrence of and sequence variation among F-specific RNA bacteriophage subgroups in feces and wastewater of urban and animal origins. Appl Environ Microbiol 2015;81:6505-6515.
  28. Weiner AM, Weber K: Natural read-through at the UGA termination signal of Qβ coat protein cistron. Nat New Biol 1971;234:206-209.
  29. Hofstetter H, Monstein HJ, Weissmann C: The readthrough protein A1 is essential for the formation of viable Qβ particles. Biochim Biophys Acta 1974;374:238-251.
  30. Engelberg-Kulka H, Dekel L, Israeli-Reches M: Streptomycin-resistant Escherichia coli mutant temperature sensitive for the production of Qβ-infective particles. J Virol 1977;21:1-6.
    External Resources
  31. Engelberg-Kulka H, Israeli-Reches M, Dekel L, Friedmann A: Qβ-defective particles produced in a streptomycin-resistant Escherichia coli mutant. J Virol 1979;29:1107-1117.
    External Resources
  32. Skamel C, Aller SG, Bopda Waffo A: In vitro evolution and affinity-maturation with coliphage Qβ display. PLoS One 2014;9:e113069.
  33. Bollback JP, Huelsenbeck JP: Phylogeny, genome evolution, and host specificity of single-stranded RNA bacteriophage (family Leviviridae). J Mol Evol 2001;52:117-128.
  34. Goessens WH, Driessen AJ, Wilschut J, van Duin J: A synthetic peptide corresponding to the C-terminal 25 residues of phage MS2 coded lysis protein dissipates the protonmotive force in Escherichia coli membrane vesicles by generating hydrophilic pores. EMBO J 1988;7:867-873.
    External Resources
  35. Pierrel J: An RNA phage Lab: MS2 in Walter Fiers' laboratory of molecular biology in Ghent, from genetic code to gene and genome, 1963-1976. J Hist Biol 2012;45:109-138.
  36. Fiers W, Contreras R, Duerinck F, Haegeman G, Iserentant D, Merregaert J, Min Jou W, Molemans F, Raeymaekers A, van den Berghe A, Volckaert G, Ysebaert M: Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene. Nature 1976;260:500-507.
  37. Crowther RA, Amos LA, Finch JT: Three-dimensional image reconstructions of bacteriophages R17 and f2. J Mol Biol 1975;98:631-635.
  38. Caspar DL, Klug A: Physical principles in the construction of regular viruses. Cold Spring Harb Symp Quant Biol 1962;27:1-24.
  39. Coleman J, Hirashima A, Inokuchi Y, Green PJ, Inouye M: A novel immune system against bacteriophage infection using complementary RNA (micRNA). Nature 1985;315:601-603.
  40. Hirashima A, Sawaki S, Inokuchi Y, Inouye M: Engineering of the mRNA-interfering complementary RNA immune system against viral infection. Proc Natl Acad Sci USA 1986;83:7726-7730.
  41. Krivisky AS, Cherban TP: Comparative study of the lethal and mutagenic action of chemical agents and radiations on the MS2 bacteriophage and its infectious RNA (in French). Arch Roum Pathol Exp Microbiol 1969;28:866-876.
    External Resources
  42. Wigginton KR, Pecson BM, Sigstam T, Bosshard F, Kohn T: Virus inactivation mechanisms: impact of disinfectants on virus function and structural integrity. Environ Sci Technol 2012;46:12069-12078.
  43. Kimmitt PT, Redway KF: Evaluation of the potential for virus dispersal during hand drying: a comparison of three methods. J Appl Microbiol 2016;120:478-486.
  44. Tomas ME, Kundrapu S, Thota P, Sunkesula VC, Cadnum JL, Mana TS, Jencson A, O'Donnell M, Zabarsky TF, Hecker MT, Ray AJ, Wilson BM, Donskey CJ: Contamination of health care personnel during removal of personal protective equipment. JAMA Intern Med 2015;175:1904-1910.
  45. Verbyla ME, Mihelcic JR: A review of virus removal in wastewater treatment pond systems. Water Res 2015;71:107-124.
  46. McAlister M, Aranha H, Larson R: Use of bacteriophages as surrogates for mammalian viruses. Dev Biol (Basel) 2004;118:89-98.
    External Resources
  47. Sinclair RG, Rose JB, Hashsham SA, Gerba CP, Haas CN: Criteria for selection of surrogates used to study the fate and control of pathogens in the environment. Appl Environ Microbiol 2012;78:1969-1977.
  48. Liu J, Ochieng C, Wiersma S, Ströher U, Towner JS, Whitmer S, Nichol ST, Moore CC, Kersh GJ, Kato C, Sexton C, Petersen J, Massung R, Hercik C, Crump JA, Kibiki G, Maro A, Mujaga B, Gratz J, Jacob ST, Banura P, Scheld WM, Juma B, Onyango CO, Montgomery JM, Houpt E, Fields B: Development of a TaqMan array card for acute-febrile-illness outbreak investigation and surveillance of emerging pathogens, including Ebola virus. J Clin Microbiol 2016;54:49-58.
  49. Lodish HF: Translational control of protein synthesis: the early years. J Biol Chem 2012;287:36528-36535.
  50. Pumpen PP, Gren EJ: Role of protein synthesis in the regulation of replication of RNA-containing bacteriophages (in Russian). Dokl Akad Nauk SSSR 1975;224:246-248.
    External Resources
  51. Pumpen P, Bauman V, Dishler A, Gren EJ: Control of replication in RNA bacteriophages. J Virol 1978;28:725-735.
    External Resources
  52. Lampasona AA, Czaplinski K: RNA voyeurism: a coming of age story. Methods 2016;98:10-17.
  53. Bensidoun P, Raymond P, Oeffinger M, Zenklusen D: Imaging single mRNAs to study dynamics of mRNA export in the yeast Saccharomyces cerevisiae. Methods 2016;98:104-114.
  54. Gong C, Maquat LE: Affinity purification of long noncoding RNA-protein complexes from formaldehyde cross-linked mammalian cells. Methods Mol Biol 2015;1206:81-86.
  55. Hocine S, Raymond P, Zenklusen D, Chao JA, Singer RH: Single-molecule analysis of gene expression using two-color RNA labeling in live yeast. Nat Methods 2013;10:119-121.
  56. Bardwell VJ, Wickens M: Purification of RNA and RNA-protein complexes by an R17 coat protein affinity method. Nucleic Acids Res 1990;18:6587-6594.
  57. Dahlman JE, Abudayyeh OO, Joung J, Gootenberg JS, Zhang F, Konermann S: Orthogonal gene knockout and activation with a catalytically active Cas9 nuclease. Nat Biotechnol 2015;33:1159-1161.
  58. Remaut E, Waele PD, Marmenout A, Stanssens P, Fiers W: Functional expression of individual plasmid-coded RNA bacteriophage MS2 genes. EMBO J 1982;1:205-209.
    External Resources
  59. Kastelein RA, Berkhout B, Overbeek GP, van Duin J: Effect of the sequences upstream from the ribosome-binding site on the yield of protein from the cloned gene for phage MS2 coat protein. Gene 1983;23:245-254.
  60. Kozlovskaia TM, Pumpen PP, Dreilinia DE, Tsimanis AIu, Ose VP,Tsibinogin VV, Gren EJ: Formation of capsid-like structures as a result of expression of the cloned gene of the envelope protein of the RNA-containing bacteriophage fr (in Russian). Dokl Akad Nauk SSSR 1986;287:452-455.
    External Resources
  61. Adhin MR, Hirashima A, van Duin J: Nucleotide sequence from the ssRNA bacteriophage JP34 resolves the discrepancy between serological and biophysical classification. Virology 1989;170:238-242.
  62. Ni CZ, White CA, Mitchell RS, Wickersham J, Kodandapani R, Peabody DS, Ely KR: Crystal structure of the coat protein from the GA bacteriophage: model of the unassembled dimer. Protein Sci 1996;5:2485-2493.
  63. Kozlovska TM, Cielens I, Dreilina D, Dislers A, Baumanis V, Ose V, Pumpens P: Recombinant RNA phage Qβ capsid particles synthesized and self-assembled in Escherichia coli. Gene 1993;137:133-137.
  64. Priano C, Arora R, Butke J, Mills DR: A complete plasmid-based complementation system for RNA coliphage Qβ: three proteins of bacteriophages Qβ (group III) and SP (group IV) can be interchanged. J Mol Biol 1995;249:283-297.
  65. Lim F, Downey TP, Peabody DS: Translational repression and specific RNA binding by the coat protein of the Pseudomonas phage PP7. J Biol Chem 2001;276:22507-22513.
  66. Caldeira JC, Peabody DS: Stability and assembly in vitro of bacteriophage PP7 virus-like particles. J Nanobiotechnol 2007;5:10.
  67. Tissot AC, Renhofa R, Schmitz N, Cielens I, Meijerink E, Ose V, Jennings GT, Saudan P, Pumpens P, Bachmann MF: Versatile virus-like particle carrier for epitope based vaccines. PLoS One 2010;5:e9809.
  68. Spohn G, Jennings GT, Martina BE, Keller I, Beck M, Pumpens P, Osterhaus AD, Bachmann MF: A VLP-based vaccine targeting domain III of the West Nile virus E protein protects from lethal infection in mice. Virol J 2010;7:146.
  69. Persson M, Tars K, Liljas L: The capsid of the small RNA phage PRR1 is stabilized by metal ions. J Mol Biol 2008;383:914-922.
  70. Plevka P, Kazaks A, Voronkova T, Kotelovica S, Dishlers A, Liljas L, Tars K: The structure of bacteriophage φCb5 reveals a role of the RNA genome and metal ions in particle stability and assembly. J Mol Biol 2009;391:635-647.
  71. Spirin AS, Baranov VI, Ryabova LA, Ovodov SY, Alakhov YB: A continuous cell-free translation system capable of producing polypeptides in high yield. Science 1988;242:1162-1164.
  72. Bundy BC, Franciszkowicz MJ, Swartz JR: Escherichia coli-based cell-free synthesis of virus-like particles. Biotechnol Bioeng 2008;100:28-37.
  73. Rumnieks J, Ose V, Tars K, Dislers A, Strods A, Cielens I, Renhofa R: Assembly of mixed rod-like and spherical particles from group I and II RNA bacteriophage coat proteins. Virology 2009;391:187-194.
  74. Legendre D, Fastrez J: Production in Saccharomyces cerevisiae of MS2 virus-like particles packaging functional heterologous mRNAs. J Biotechnol 2005;117:183-194.
  75. Freivalds J, Dislers A, Ose V, Skrastina D, Cielens I, Pumpens P, Sasnauskas K, Kazaks A: Assembly of bacteriophage Qβ virus-like particles in yeast Saccharomyces cerevisiae and Pichia pastoris. J Biotechnol 2006;123:297-303.
  76. Freivalds J, Rumnieks J, Ose V, Renhofa R, Kazaks A: High-level expression and purification of bacteriophage GA virus-like particles from yeast Saccharomyces cerevisiae and Pichia pastoris. Acta Universitatis Latviensis Biol 2008;745:75-85.
  77. Freivalds J, Kotelovica S, Voronkova T, Ose V, Tars K, Kazaks A: Yeast-expressed bacteriophage-like particles for the packaging of nanomaterials. Mol Biotechnol 2014;56:102-110.
  78. Rossmann MG: Structure of viruses: a short history. Q Rev Biophys 2013;46:133-180.
  79. Schwartz FM, Zinder ND: Crystalline aggregates in bacterial cells infected with the RNA bacteriophage f2. Virology 1963;21:276-278.
  80. de Petris S, Nava G: Sex specific bacteriophages of E. coli K12. II. Electron microscope observations on the structure and intracellular multiplication of bacteriophage µ2. Giorn Microbiol 1963;11:1-7.
  81. Franklin RM, Granboulan N: Ultrastructure of Escherichia coli cells infected with bacteriophage R17. J Bacteriol 1966;91:834-848.
    External Resources
  82. Pumpens P, Grens E: Artificial genes for chimeric virus-like particles; in Khudyakov YE, Fields HA (eds): Artificial DNA. Methods and Applications. Boca Raton, CRC Press LLC, 2002, pp 249-327.
    External Resources
  83. Valegård K, Unge T, Montelius I, Strandberg B, Fiers W: Purification, crystallization and preliminary X-ray data of the bacteriophage MS2. J Mol Biol 1986;190:587-591.
  84. Valegård K, Liljas L, Fridborg K, Unge T: The three-dimensional structure of the bacterial virus MS2. Nature 1990;345:36-41.
  85. Valegård K, Liljas L, Fridborg K, Unge T: Structure determination of the bacteriophage MS2. Acta Crystallogr B 1991;47:949-960.
  86. Golmohammadi R, Valegård K, Fridborg K, Liljas L: The refined structure of bacteriophage MS2 at 2.8 Å resolution. J Mol Biol 1993;234:620-639.
  87. Stonehouse NJ, Valegård K, Golmohammadi R, van den Worm S, Walton C, Stockley PG, Liljas L: Crystal structures of MS2 capsids with mutations in the subunit FG loop. J Mol Biol 1996;256:330-339.
  88. Min Jou W, Raeymaekers A, Fiers W: Crystallization of bacteriophage MS2. Eur J Biochem 1979;102:589-594.
  89. Bundule M, Pumpens P, Ose V, Valegård K, Liljas L: Crystallization of bacteriophage fr and its recombinant capsids. J Mol Biol 1993;232:1005-1006.
  90. Liljas L, Fridborg K, Valegård K, Bundule M, Pumpens P: Crystal structure of bacteriophage fr capsids at 3.5 Å resolution. J Mol Biol 1994;244:279-290.
  91. Tars K, Bundule M, Fridborg K, Liljas L: The crystal structure of bacteriophage GA and a comparison of bacteriophages belonging to the major groups of Escherichia coli leviviruses. J Mol Biol 1997;271:759-773.
  92. Valegård K, Fridborg K, Liljas L: Crystallization and preliminary X-ray diffraction studies of the bacteriophage Qβ. Acta Crystallogr D Biol Crystallogr 1994;50:105-109.
  93. Golmohammadi R, Fridborg K, Bundule M, Valegård K, Liljas L: The crystal structure of bacteriophage Qβ at 3.5 Å resolution. Structure 1996;4:543-554.
  94. Tars K, Fridborg K, Bundule M, Liljas L: Structure determination of bacteriophage PP7 from Pseudomonas aeruginosa: from poor data to a good map. Acta Crystallogr D Biol Crystallogr 2000;56:398-405.
  95. Tars K, Fridborg K, Bundule M, Liljas L: The three-dimensional structure of bacteriophage PP7 from Pseudomonas aeruginosa at 3.7-Å resolution. Virology 2000;272:331-337.
  96. Lim F, Peabody DS: RNA recognition site of PP7 coat protein. Nucleic Acids Res 2002;30:4138-4144.
  97. Nap RJ, Božič AL, Szleifer I, Podgornik R: The role of solution conditions in the bacteriophage PP7 capsid charge regulation. Biophys J 2014;107:1970-1979.
  98. Hull R: The stabilization of the particles of turnip rosette virus and of other members of the southern bean mosaic virus group. Virology 1977;79:58-66.
  99. Shishovs M, Rumnieks J, Diebholder C, Jaudzems K, Kazaks A, Pintacuda G, Koning R, Tars K: Structure of AP205 coat protein reveals circular permutation in ssRNA bacteriophage. J Mol Biol. 2016;428:4267-4279.
  100. Ni CZ, Syed R, Kodandapani R, Wickersham J, Peabody DS, Ely KR: Crystal structure of the MS2 coat protein dimer: implications for RNA binding and virus assembly. Structure 1995;3:255-263.
  101. Peabody DS, Lim F: Complementation of RNA binding site mutations in MS2 coat protein heterodimers. Nucleic Acids Res 1996;24:2352-2359.
  102. Plevka P, Tars K, Liljas L: Structure and stability of icosahedral particles of a covalent coat protein dimer of bacteriophage MS2. Protein Sci 2009;18:1653-1661.
  103. Plevka P, Tars K, Liljas L: Crystal packing of a bacteriophage MS2 coat protein mutant corresponds to octahedral particles. Protein Sci 2008;17:1731-1739.
  104. Valegård K, Murray JB, Stockley PG, Stonehouse NJ, Liljas L: Crystal structure of an RNA bacteriophage coat protein-operator complex. Nature 1994;371:623-626.
  105. Stockley PG, Stonehouse NJ, Murray JB, Goodman ST, Talbot SJ, Adams CJ, Liljas L, Valegård K: Probing sequence-specific RNA recognition by the bacteriophage MS2 coat protein. Nucleic Acids Res 1995;23:2512-2518.
  106. Valegård K, Murray JB, Stonehouse NJ, van den Worm S, Stockley PG, Liljas L: The three-dimensional structures of two complexes between recombinant MS2 capsids and RNA operator fragments reveal sequence-specific protein-RNA interactions. J Mol Biol 1997;270:724-738.
  107. Lago H, Fonseca SA, Murray JB, Stonehouse NJ, Stockley PG: Dissecting the key recognition features of the MS2 bacteriophage translational repression complex. Nucleic Acids Res 1998;26:1337-1344.
  108. van den Worm SH, Stonehouse NJ, Valegård K, Murray JB, Walton C, Fridborg K, Stockley PG, Liljas L: Crystal structures of MS2 coat protein mutants in complex with wild-type RNA operator fragments. Nucleic Acids Res 1998;26:1345-1351.
  109. Peabody DS, Chakerian A: Asymmetric contributions to RNA binding by the Thr45 residues of the MS2 coat protein dimer. J Biol Chem 1999;274:25403-25410.
  110. Lim F, Spingola M, Peabody DS: Altering the RNA binding specificity of a translational repressor. J Biol Chem 1994;269:9006-9010.
    External Resources
  111. Lim F, Peabody DS: Mutations that increase the affinity of a translational repressor for RNA. Nucleic Acids Res 1994;22:3748-3752.
  112. Convery MA, Rowsell S, Stonehouse NJ, Ellington AD, Hirao I, Murray JB, Peabody DS, Phillips SE, Stockley PG: Crystal structure of an RNA aptamer-protein complex at 2.8 Å resolution. Nat Struct Biol 1998;5:133-139.
  113. Rowsell S, Stonehouse NJ, Convery MA, Adams CJ, Ellington AD, Hirao I, Peabody DS, Stockley PG, Phillips SE: Crystal structures of a series of RNA aptamers complexed to the same protein target. Nat Struct Biol 1998;5:970-975.
  114. Grahn E, Stonehouse NJ, Murray JB, van den Worm S, Valegård K, Fridborg K, Stockley PG, Liljas L: Crystallographic studies of RNA hairpins in complexes with recombinant MS2 capsids: implications for binding requirements. RNA 1999;5:131-138.
  115. Horn WT, Convery MA, Stonehouse NJ, Adams CJ, Liljas L, Phillips SE, Stockley PG: The crystal structure of a high affinity RNA stem-loop complexed with the bacteriophage MS2 capsid: further challenges in the modeling of ligand-RNA interactions. RNA 2004;10:1776-1782.
  116. Persson M, Tars K, Liljas L: PRR1 coat protein binding to its RNA translational operator. Acta Crystallogr D Biol Crystallogr 2013;69:367-372.
  117. Chao JA, Patskovsky Y, Almo SC, Singer RH: Structural basis for the coevolution of a viral RNA-protein complex. Nat Struct Mol Biol 2008;15:103-105.
  118. Rumnieks J, Tars K: Crystal structure of the bacteriophage Qβ coat protein in complex with the RNA operator of the replicase gene. J Mol Biol 2014;426:1039-1049.
  119. Koning R, van den Worm S, Plaisier JR, van Duin J, Pieter Abrahams J, Koerten H: Visualization by cryo-electron microscopy of genomic RNA that binds to the protein capsid inside bacteriophage MS2. J Mol Biol 2003;332:415-422.
  120. Toropova K, Basnak G, Twarock R, Stockley PG, Ranson NA: The three-dimensional structure of genomic RNA in bacteriophage MS2: implications for assembly. J Mol Biol 2008;375:824-836.
  121. Rolfsson Ó, Middleton S, Manfield IW, White SJ, Fan B, Vaughan R, Ranson NA, Dykeman E, Twarock R, Ford J, Cheng Kao C, Stockley PG: Direct evidence for packaging signal-mediated assembly of bacteriophage MS2. J Mol Biol 2016;428:431-448.
  122. Stockley PG, White SJ, Dykeman E, Manfield I, Rolfsson O, Patel N, Bingham R, Barker A, Wroblewski E, Chandler-Bostock R, Weiß EU, Ranson NA, Tuma R, Twarock R: Bacteriophage MS2 genomic RNA encodes an assembly instruction manual for its capsid. Bacteriophage 2016;6:e1157666.
  123. Dent KC, Thompson R, Barker AM, Hiscox JA, Barr JN, Stockley PG, Ranson NA: The asymmetric structure of an icosahedral virus bound to its receptor suggests a mechanism for genome release. Structure 2013;21:1225-1234.
  124. Koning RI, Gomez-Blanco J, Akopjana I, Vargas J, Kazaks A, Tars K, Carazo JM, Koster AJ: Asymmetric cryo-EM reconstruction of phage MS2 reveals genome structure in situ. Nat Commun 2016;7:12524.
  125. Kuzmanovic DA, Elashvili I, Wick C, O'Connell C, Krueger S: The MS2 coat protein shell is likely assembled under tension: a novel role for the MS2 bacteriophage A protein as revealed by small-angle neutron scattering. J Mol Biol 2006;355:1095-1111.
  126. Rowlands DT Jr: Precipitation and neutralization of bacteriophage f2 by rabbit antibodies. J Immunol 1967;98:958-964.
    External Resources
  127. Rappaport I: An analysis of the inactivation of MS2 bacteriophage with antiserum. J Gen Virol 1970;6:25-32.
  128. Rohrmann GF, Krueger RG: Precipitation and neutralization of bacteriophage MS-2 by rabbit antibodies. J Immunol 1970;104:353-358.
    External Resources
  129. Krueger RG: Effect of antigenic stimulation on the specificity of antibody produced by rabbits immunized with bacteriophage MS-2. J Immunol 1970;104:1117-1123.
    External Resources
  130. Snippe H, de Reuver MJ, Belder M, Willers JM: Bacteriophage MS-2 in the immune response. Int Arch Allergy Appl Immunol 1976;50:111-122.
  131. Langbeheim H, Teitelbaum D, Arnon R: Cellular immune response toward MS-2 phage and a synthetic fragment of its coat protein. Cell Immunol 1978;38:193-197.
  132. Langbeheim H, Arnon R, Sela M: Antiviral effect on MS-2 coliphage obtained with a synthetic antigen. Proc Natl Acad Sci USA 1976;73:4636-4640.
  133. Langbeheim H, Arnon R, Sela M: Adjuvant effect of a peptidoglycan attached covalently to a synthetic antigen provoking anti-phage antibodies. Immunology 1978;35:573-579.
    External Resources
  134. Arnon R, Sela M, Parant M, Chedid L: Antiviral response elicited by a completely synthetic antigen with built-in adjuvanticity. Proc Natl Acad Sci USA 1980;77:6769-6772.
  135. Steinbergs J, Kilchewska K, Lazdina U, Dishlers A, Ose V, Sällberg M, Tsimanis A: Short synthetic CDR-peptides forming the antibody combining site of the monoclonal antibody against RNA bacteriophage fr neutralize the phage activity. Hum Antibodies Hybridomas 1996;7:106-112.
    External Resources
  136. Liu JL, Zabetakis D, Goldman ER, Anderson GP: Selection and evaluation of single domain antibodies toward MS2 phage and coat protein. Mol Immunol 2013;53:118-125.
  137. Borisova G., Bundule M, Grinstein E, Dreilina D, Dreimane A, Kalis J, Kozlovskaya T, Loseva V, Ose V, Pumpen P, Pushko P, Snikere D, Stankevica E, Tsibinogin V, Gren EJ: Recombinant capsid structures for exposure of protein antigenic epitopes. Mol Gen (Life Sci Adv) 1987;6:169-174.
  138. Gren EJ, Pumpen P: Recombinant viral capsids as a new age of immunogenic proteins and vaccines (in Russian). J All Union Mendeleyevs Chem Soc 1988;33:531-536.
  139. Mastico RA, Talbot SJ, Stockley PG: Multiple presentation of foreign peptides on the surface of an RNA-free spherical bacteriophage capsid. J Gen Virol 1993;74:541-548.
  140. Kozlovskaia TM, Pushko PM, Stankevich EI, Dreimane AIa, Sniker DIa, Grinstein EE, Dreilinia DE, Veinia AE, Ose VP, Pumpen P, Gren EJ: Genetically engineered mutants of the envelope protein of the RNA-containing bacteriophage fr (in Russian). Mol Biol 1988;22:731-740.
    External Resources
  141. Pushko P, Kozlovskaya T, Sominskaya I, Brede A, Stankevica E, Ose V, Pumpens P, Grens E: Analysis of RNA phage fr coat protein assembly by insertion, deletion and substitution mutagenesis. Protein Eng 1993;6:883-891.
  142. Axblom C, Tars K, Fridborg K, Orna L, Bundule M, Liljas L: Structure of phage fr capsids with a deletion in the FG loop: implications for viral assembly. Virology 1998;249:80-88.
  143. Stonehouse NJ, Stockley PG: Effects of amino acid substitution on the thermal stability of MS2 capsids lacking genomic RNA. FEBS Lett 1993;334:355-359.
  144. Peabody DS: Subunit fusion confers tolerance to peptide insertions in a virus coat protein. Arch Biochem Biophys 1997;347:85-92.
  145. Heal KG, Hill HR, Stockley PG, Hollingdale MR, Taylor-Robinson AW: Expression and immunogenicity of a liver stage malaria epitope presented as a foreign peptide on the surface of RNA-free MS2 bacteriophage capsids. Vaccine 2000;18:251-258.
  146. Voronkova T, Grosch A, Kazaks A, Ose V, Skrastina D, Sasnauskas K, Jandrig B, Arnold W, Scherneck S, Pumpens P, Ulrich R: Chimeric bacteriophage fr virus-like particles harboring the immunodominant C-terminal region of hamster polyomavirus VP1 induce a strong VP1-specific antibody response in mice. Viral Immunol 2002;15:627-643.
  147. Pumpens P, Razanskas R, Pushko P, Renhof R, Gusars I, Skrastina D, Ose V, Borisova G, Sominskaya I, Petrovskis I, Jansons J, Sasnauskas K: Evaluation of HBs, HBc, and frCP virus-like particles for expression of human papillomavirus 16 E7 oncoprotein epitopes. Intervirology 2002;45:24-32.
  148. Kozlovska TM, Cielens I, Vasiljeva I, Strelnikova A, Kazaks A, Dislers A, Dreilina D, Ose V, Gusars I, Pumpens P: RNA phage Qβ coat protein as a carrier for foreign epitopes. Intervirology 1996;39:9-15.
    External Resources
  149. Kozlovska TM, Cielens I, Vasiljeva I, Bundule M, Strelnikova A, Kazaks A, Dislers A, Dreilina D, Ose V, Gusars I, Pumpens P: Display vectors. II. Recombinant capsid of RNA bacteriophage Qβ as a display moiety. Proc Latv Acad Sci 1997;51:8-12.
  150. Rumnieks J, Tars K: Crystal structure of the read-through domain from bacteriophage Qβ A1 protein. Protein Sci 2011;20:1707-1712.
  151. Smiley BK, Minion FC: Enhanced readthrough of opal (UGA) stop codons and production of Mycoplasma pneumoniae P1 epitopes in Escherichia coli. Gene 1993;134:33-40.
  152. Vasiljeva I, Kozlovska T, Cielens I, Strelnikova A, Kazaks A, Ose V, Pumpens P: Mosaic Qβ coats as a new presentation model. FEBS Lett 1998;431:7-11.
  153. Fehr T, Skrastina D, Pumpens P, Zinkernagel RM: T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant virus particles. Proc Natl Acad Sci USA 1998;95:9477-9481.
  154. Lim F, Spingola M, Peabody DS: The RNA-binding site of bacteriophage Qβ coat protein. J Biol Chem 1996;271:31839-31845.
  155. Spingola M, Peabody DS: MS2 coat protein mutants which bind Qβ RNA. Nucleic Acids Res 1997;25:2808-2815.
  156. Pickett GG, Peabody DS: Encapsidation of heterologous RNAs by bacteriophage MS2 coat protein. Nucleic Acids Res 1993;21:4621-4626.
  157. Cielens I, Ose V, Petrovskis I, Strelnikova A, Renhofa R, Kozlovska T, Pumpens P: Mutilation of RNA phage Qβ virus-like particles: from icosahedrons to rods. FEBS Lett 2000;482:261-264.
  158. van Meerten D, Olsthoorn RC, van Duin J, Verhaert RM: Peptide display on live MS2 phage: restrictions at the RNA genome level. J Gen Virol 2001;82:1797-1805.
  159. Peabody DS, Manifold-Wheeler B, Medford A, Jordan SK, do Carmo Caldeira J, Chackerian B: Immunogenic display of diverse peptides on virus-like particles of RNA phage MS2. J Mol Biol 2008;380:252-263.
  160. Chackerian B, Caldeira Jdo C, Peabody J, Peabody DS: Peptide epitope identification by affinity selection on bacteriophage MS2 virus-like particles. J Mol Biol 2011;409:225-237.
  161. Sominskaya I, Pushko P, Dreilina D, Kozlovskaya T, Pumpens P: Determination of the minimal length of preS1 epitope recognized by a monoclonal antibody which inhibits attachment of hepatitis B virus to hepatocytes. Med Microbiol Immunol 1992;181:215-226.
  162. Sominskaya I, Bichko V, Pushko P, Dreimane A, Snikere D, Pumpens P: Tetrapeptide QDPR is a minimal immunodominant epitope within the preS2 domain of hepatitis B virus. Immunol Lett 1992;33:169-172.
  163. Sällberg M, Pushko P, Berzinsh I, Bichko V, Sillekens P, Noah M, Pumpens P, Grens E, Wahren B, Magnius LO: Immunochemical structure of the carboxy-terminal part of hepatitis B e antigen: identification of internal and surface-exposed sequences. J Gen Virol 1993;74:1335-1340.
  164. Meisel H, Sominskaya I, Pumpens P, Pushko P, Borisova G, Deepen R, Lu X, Spiller GH, Kruger DH, Grens E, Gerlich WH: Fine-mapping and functional characterization of two immuno-dominant regions from the preS2 sequence of hepatitis B virus. Intervirology 1994;275:330-339.
    External Resources
  165. Sobotta D, Sominskaya I, Jansons J, Meisel H, Schmitt S, Heermann K-H, Kaluza G, Pumpens P, Gerlich WH: Mapping of immunodominant B-cell epitopes and the human serum albumin-binding site in natural hepatitis B virus surface antigen of defined genosubtype. J Gen Virol 2000;81:369-378.
  166. Sominskaya I, Paulij W, Jansons J, Sobotta D, Dreilina D, Sunnen C, Meisel H, Gerlich WH, Pumpens P: Fine-mapping of the B-cell epitope domain at the N-terminus of the preS2 region of the hepatitis B surface antigen. J Immunol Meth 2002;260:251-261.
  167. Jegerlehner A, Storni T, Lipowsky G, Schmid M, Pumpens P, Bachmann MF: Regulation of IgG antibody responses by epitope density and CD21-mediated costimulation. Eur J Immunol 2002;32:3305-3314.
  168. Jegerlehner A, Tissot A, Lechner F, Sebbel P, Erdmann I, Kündig T, Bächi T, Storni T, Jennings G, Pumpens P, Renner WA, Bachmann MF: A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses. Vaccine 2002;20:3104-3112.
  169. Bachmann MF, Dyer MR: Therapeutic vaccination for chronic diseases: a new class of drugs in sight. Nat Rev Drug Discov 2004;3:81-88.
  170. Dyer MR, Renner WA, Bachmann MF: A second vaccine revolution for the new epidemics of the 21st century. Drug Discov Today 2006;11:1028-1033.
  171. Bachmann MF, Jennings GT: Therapeutic vaccines for chronic diseases: successes and technical challenges. Philos Trans R Soc Lond B Biol Sci 2011;366:2815-2822.
  172. Peabody DS: A viral platform for chemical modification and multivalent display. J Nanobiotechnol 2003;1:5.
  173. Cheng YJ, Liang JX, Li QG: Construction of RNA-containing virus-like nanoparticles expression vector with cysteine residues on surface and fluorescent decoration (in Chinese). Yi Chuan Xue Bao 2005;32:874-878.
    External Resources
  174. Patel KG, Swartz JR: Surface functionalization of virus-like particles by direct conjugation using azide-alkyne click chemistry. Bioconjug Chem 2011;22:376-387.
  175. Hooker JM, Kovacs EW, Francis MB: Interior surface modification of bacteriophage MS2. J Am Chem Soc 2004;126:3718-3719.
  176. Cheng Y, Niu J, Zhang Y, Huang J, Li Q: Preparation of His-tagged armored RNA phage particles as a control for real-time reverse transcription-PCR detection of severe acute respiratory syndrome coronavirus. J Clin Microbiol 2006;44:3557-3561.
  177. Udit AK, Brown S, Baksh MM, Finn MG: Immobilization of bacteriophage Qβ on metal-derivatized surfaces via polyvalent display of hexahistidine tags. J Inorg Biochem 2008;102:2142-2146.
  178. Udit AK, Hollingsworth W, Choi K: Metal- and metallocycle-binding sites engineered into polyvalent virus-like scaffolds. Bioconjug Chem 2010;21:399-404.
  179. Strable E, Prasuhn DE Jr, Udit AK, Brown S, Link AJ, Ngo JT, Lander G, Quispe J, Potter CS, Carragher B, Tirrell DA, Finn MG: Unnatural amino acid incorporation into virus-like particles. Bioconjug Chem 2008;19:866-875.
  180. Smith MT, Varner CT, Bush DB, Bundy BC: The incorporation of the A2 protein to produce novel Qβ virus-like particles using cell-free protein synthesis. Biotechnol Prog 2012;28:549-555.
  181. Brune KD, Leneghan DB, Brian IJ, Ishizuka AS, Bachmann MF, Draper SJ, Biswas S, Howarth M: Plug-and-display: decoration of virus-like particles via isopeptide bonds for modular immunization. Sci Rep 2016;6:19234.
  182. Thrane S, Janitzek CM, Matondo S, Resende M, Gustavsson T, de Jongh WA, Clemmensen S, Roeffen W, van de Vegte-Bolmer M, van Gemert GJ, Sauerwein R, Schiller JT, Nielsen MA, Theander TG, Salanti A, Sander AF: Bacterial superglue enables easy development of efficient virus-like particle based vaccines. J Nanobiotechnol 2016;14:30.
  183. Zakeri B, Fierer JO, Celik E, Chittock EC, Schwarz-Linek U, Moy VT, Howarth M: Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin. Proc Natl Acad Sci USA 2012;109:E690-E697.
  184. Veggiani G, Zakeri B, Howarth M: Superglue from bacteria: unbreakable bridges for protein nanotechnology. Trends Biotechnol 2014;32:506-512.
  185. Peabody DS, Al-Bitar L: Isolation of viral coat protein mutants with altered assembly and aggregation properties. Nucleic Acids Res 2001;29:E113.
  186. Lima SM, Peabody DS, Silva JL, de Oliveira AC: Mutations in the hydrophobic core and in the protein-RNA interface affect the packing and stability of icosahedral viruses. Eur J Biochem 2004;271:135-145.
  187. Ashcroft AE, Lago H, Macedo JM, Horn WT, Stonehouse NJ, Stockley PG: Engineering thermal stability in RNA phage capsids via disulphide bonds. J Nanosci Nanotechnol 2005;5:2034-2041.
  188. Bundy BC, Swartz JR: Efficient disulfide bond formation in virus-like particles. J Biotechnol 2011;154:230-239.
  189. Fiedler JD, Higginson C, Hovlid ML, Kislukhin AA, Castillejos A, Manzenrieder F, Campbell MG, Voss NR, Potter CS, Carragher B, Finn MG: Engineered mutations change the structure and stability of a virus-like particle. Biomacromolecules 2012;13:2339-2348.
  190. Caldeira JC, Peabody DS: Thermal stability of RNA phage virus-like particles displaying foreign peptides. J Nanobiotechnol 2011;9:22.
  191. Caldeira Jdo C, Medford A, Kines RC, Lino CA, Schiller JT, Chackerian B, Peabody DS: Immunogenic display of diverse peptides, including a broadly cross-type neutralizing human papillomavirus L2 epitope, on virus-like particles of the RNA bacteriophage PP7. Vaccine 2010;28:4384-4393.
  192. Temizoz B, Kuroda E, Ishii KJ: Vaccine adjuvants as potential cancer immunotherapeutics. Int Immunol 2016;28:329-338.
  193. Brencicova E, Diebold SS: Nucleic acids and endosomal pattern recognition: how to tell friend from foe? Front Cell Infect Microbiol 2013;3:37.
  194. Jennings GT, Bachmann MF: Designing recombinant vaccines with viral properties: a rational approach to more effective vaccines. Curr Mol Med 2007;7:143-155.
  195. Chackerian B: Virus-like particles: flexible platforms for vaccine development. Expert Rev Vaccines 2007;6:381-390.
  196. Jennings GT, Bachmann MF: The coming of age of virus-like particle vaccines. Biol Chem 2008;389:521-536.
  197. Bachmann MF, Jennings GT: Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 2010;10:787-796.
  198. Pushko P, Pumpens P, Grens E: Development of virus-like particle technology from small highly symmetric to large complex virus-like particle structures. Intervirology 2013;56:141-165.
  199. Diederich S, Gedvilaite A, Zvirbliene A, Kazaks A, Sasnauskas K, Johnson N, Ulrich RG: Virus-like particles: a versatile tool for basic and applied research on emerging and reemerging viruses; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 137-160.
    External Resources
  200. Lundstrom K: Cancer therapy applying viral nanoparticles; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 455-466.
    External Resources
  201. Bachmann MF, Zabel F: Immunology of virus-like particles; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 121-128.
    External Resources
  202. Lee KL, Twyman RM, Fiering S, Steinmetz NF: Virus-based nanoparticles as platform technologies for modern vaccines. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016;8:554-578.
  203. Chackerian B, Peabody DS: Bacteriophage virus-like particles as a platform for vaccine discovery; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 239-250.
    External Resources
  204. Fu Y, Li J: A novel delivery platform based on bacteriophage MS2 virus-like particles. Virus Res 2016;211:9-16.
  205. Tumban E, Peabody J, Peabody DS, Chackerian B: A pan-HPV vaccine based on bacteriophage PP7 VLPs displaying broadly cross-neutralizing epitopes from the HPV minor capsid protein, L2. PLoS One 2011;6:e23310.
  206. Hunter Z, Tumban E, Dziduszko A, Chackerian B: Aerosol delivery of virus-like particles to the genital tract induces local and systemic antibody responses. Vaccine 2011;29:4584-4592.
  207. Tumban E, Peabody J, Peabody DS, Chackerian B: A universal virus-like particle-based vaccine for human papillomavirus: longevity of protection and role of endogenous and exogenous adjuvants. Vaccine 2013;31:4647-4654.
  208. Tyler M, Tumban E, Dziduszko A, Ozbun MA, Peabody DS, Chackerian B: Immunization with a consensus epitope from human papillomavirus L2 induces antibodies that are broadly neutralizing. Vaccine 2014;32:4267-4274.
  209. Tyler M, Tumban E, Peabody DS, Chackerian B: The use of hybrid virus-like particles to enhance the immunogenicity of a broadly protective HPV vaccine. Biotechnol Bioeng 2014;111:2398-2406.
  210. Tumban E, Muttil P, Escobar CA, Peabody J, Wafula D, Peabody DS, Chackerian B: Preclinical refinements of a broadly protective VLP-based HPV vaccine targeting the minor capsid protein, L2. Vaccine 2015;33:3346-3353.
  211. Tumban E, Peabody J, Tyler M, Peabody DS, Chackerian B: VLPs displaying a single L2 epitope induce broadly cross-neutralizing antibodies against human papillomavirus. PLoS One 2012;7:e49751.
  212. Jiang RT, Schellenbacher C, Chackerian B, Roden RB: Progress and prospects for L2-based human papillomavirus vaccines. Expert Rev Vaccines 2016;10:1-10.
  213. Ord RL, Caldeira JC, Rodriguez M, Noe A, Chackerian B, Peabody DS, Gutierrez G, Lobo CA: A malaria vaccine candidate based on an epitope of the Plasmodium falciparum RH5 protein. Malar J 2014;13:326.
  214. Crossey E, Frietze K, Narum DL, Peabody DS, Chackerian B: Identification of an immunogenic mimic of a conserved epitope on the Plasmodium falciparum blood stage antigen AMA1 using virus-like particle (VLP) peptide display. PLoS One 2015;10:e0132560.
  215. Cielens I, Jackevica L, Strods A, Kazaks A, Ose V, Bogans J, Pumpens P, Renhofa R: Mosaic RNA phage VLPs carrying domain III of the West Nile virus E protein. Mol Biotechnol 2014;56:459-469.
  216. Bachmann MF, Rohrer UH, Kündig TM, Bürki K, Hengartner H, Zinkernagel RM: The influence of antigen organization on B cell responsiveness. Science 1993;262:1448-1451.
  217. Senti G, Johansen P, Haug S, Bull C, Gottschaller C, Müller P, Pfister T, Maurer P, Bachmann MF, Graf N, Kündig TM: Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial. Clin Exp Allergy 2009;39:562-570.
  218. Klimek L, Willers J, Hammann-Haenni A, Pfaar O, Stocker H, Mueller P, Renner WA, Bachmann MF: Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study. Clin Exp Allergy 2011;41:1305-1312.
  219. Klimek L, Schendzielorz P, Mueller P, Saudan P, Willers J: Immunotherapy of allergic rhinitis: new therapeutic opportunities with virus-like particles filled with CpG motifs. Am J Rhinol Allergy 2013;27:206-212.
  220. Beeh KM, Kanniess F, Wagner F, Schilder C, Naudts I, Hammann-Haenni A, Willers J, Stocker H, Mueller P, Bachmann MF, Renner WA: The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma. J Allergy Clin Immunol 2013;131:866-874.
  221. Casale TB, Cole J, Beck E, Vogelmeier CF, Willers J, Lassen C, Hammann-Haenni A, Trokan L, Saudan P, Wechsler ME: CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled phase 2b study. Allergy 2015;70:1160-1168.
  222. Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann MF: Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J Immunol 2004;172:1777-1785.
  223. Bachmann MF, Schwarz K, Wolint P, Meijerink E, Martin S, Manolova V, Oxenius A: Cutting edge: distinct roles for T help and CD40/CD40 ligand in regulating differentiation of proliferation-competent memory CD8+ T cells. J Immunol 2004;173:2217-2221.
  224. Schwarz K, Meijerink E, Speiser DE, Tissot AC, Cielens I, Renhof R, Dishlers A, Pumpens P, Bachmann MF: Efficient homologous prime-boost strategies for T cell vaccination based on virus-like particles. Eur J Immunol 2005;35:816-821.
  225. Bachmann MF, Wolint P, Schwarz K, Jäger P, Oxenius A: Functional properties and lineage relationship of CD8+ T cell subsets identified by expression of IL-7 receptor α and CD62L. J Immunol 2005;175:4686-4696.
  226. Bessa J, Schmitz N, Hinton HJ, Schwarz K, Jegerlehner A, Bachmann MF: Efficient induction of mucosal and systemic immune responses by virus-like particles administered intranasally: implications for vaccine design. Eur J Immunol 2008;38:114-126.
  227. Agnellini P, Wiesel M, Schwarz K, Wolint P, Bachmann MF, Oxenius A: Kinetic and mechanistic requirements for helping CD8 T cells. J Immunol 2008;180:1517-1525.
  228. Keller SA, Bauer M, Manolova V, Muntwiler S, Saudan P, Bachmann MF: Cutting edge: limited specialization of dendritic cell subsets for MHC class II-associated presentation of viral particles. J Immunol 2010;184:26-29.
  229. Keller SA, Schwarz K, Manolova V, von Allmen CE, Kinzler MG, Bauer M, Muntwiler S, Saudan P, Bachmann MF: Innate signaling regulates cross-priming at the level of DC licensing and not antigen presentation. Eur J Immunol 2010;40:103-112.
  230. Jegerlehner A, Wiesel M, Dietmeier K, Zabel F, Gatto D, Saudan P, Bachmann MF: Carrier induced epitopic suppression of antibody responses induced by virus-like particles is a dynamic phenomenon caused by carrier-specific antibodies. Vaccine 2010;28:5503-5512.
  231. Maurer P, Jennings GT, Willers J, Rohner F, Lindman Y, Roubicek K, Renner WA, Müller P, Bachmann MF: A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity. Eur J Immunol 2005;35:2031-2040.
  232. Cornuz J, Zwahlen S, Jungi WF, Osterwalder J, Klingler K, van Melle G, Bangala Y, Guessous I, Müller P, Willers J, Maurer P, Bachmann MF, Cerny T: A vaccine against nicotine for smoking cessation: a randomized controlled trial. PLoS One 2008;3:e2547.
  233. Beerli RR, Bauer M, Buser RB, Gwerder M, Muntwiler S, Maurer P, Saudan P, Bachmann MF: Isolation of human monoclonal antibodies by mammalian cell display. Proc Natl Acad Sci USA 2008;105:14336-14341.
  234. Lang R, Winter G, Vogt L, Zurcher A, Dorigo B, Schimmele B: Rational design of a stable, freeze-dried virus-like particle-based vaccine formulation. Drug Dev Ind Pharm 2009;35:83-97.
  235. Yin Z, Comellas-Aragones M, Chowdhury S, Bentley P, Kaczanowska K, Benmohamed L, Gildersleeve JC, Finn MG, Huang X: Boosting immunity to small tumor-associated carbohydrates with bacteriophage Qβ capsids. ACS Chem Biol 2013;8:1253-1262.
  236. Yin Z, Dulaney S, McKay CS, Baniel C, Kaczanowska K, Ramadan S, Finn MG, Huang X: Chemical synthesis of GM2 glycans, bioconjugation with bacteriophage Qβ, and the induction of anticancer antibodies. Chembiochem 2016;17:174-180.
  237. Chackerian B, Frietze KM: Moving towards a new class of vaccines for non-infectious chronic diseases. Expert Rev Vaccines 2016;15:561-563.
  238. Klimek L, Willers J, Schendzielorz P, Kündig TM, Senti G: Immuntherapie der allergischen Rhinitis ohne Allergene? Neue Möglichkeiten einer Immunmodulation durch Vakzinierung mittels ‘virus-like particles' und CpG-Motiven. HNO 2013;61:826-833.
  239. Klimek L, Pfaar O: A comparison of immunotherapy delivery methods for allergen immunotherapy. Expert Rev Clin Immunol 2013;9:465-474, quiz 475.
  240. Klimek L, Bachmann MF, Senti G, Kündig TM: Immunotherapy of type-1 allergies with virus-like particles and CpG-motifs. Expert Rev Clin Immunol 2014;10:1059-1067.
  241. Fettelschoss A, Zabel F, Bachmann MF: Vaccination against Alzheimer disease: an update on future strategies. Hum Vaccin Immunother 2014;10:847-851.
  242. Gradman AH, Pinto R: Vaccination: a novel strategy for inhibiting the renin-angiotensin-aldosterone system. Curr Hypertens Rep 2008;10:473-479.
  243. Miller SA, Accardi JR, St Onge EL: Angiotensin II vaccine: a novel approach in the treatment of hypertension. Expert Opin Biol Ther 2008;8:1669-1673.
  244. Phisitkul S: CYT-006-AngQb, a vaccine against angiotensin II for the potential treatment of hypertension. Curr Opin Investig Drugs 2009;10:269-275.
    External Resources
  245. Sączyńska V: Influenza virus hemagglutinin as a vaccine antigen produced in bacteria. Acta Biochim Pol 2014;61:561-572.
    External Resources
  246. Pushko P, Tumpey TM: Traditional and novel trends in influenza vaccines; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 419-447.
    External Resources
  247. Reyes-Sandoval A, Bachmann MF: Plasmodium vivax malaria vaccines: why are we where we are? Hum Vaccin Immunother 2013;9:2558-2565.
  248. Heading CE: Drug evaluation: CYT-002-NicQb, a therapeutic vaccine for the treatment of nicotine addiction. Curr Opin Investig Drugs 2007;8:71-77.
    External Resources
  249. Maurer P, Bachmann MF: Vaccination against nicotine: an emerging therapy for tobacco dependence. Expert Opin Investig Drugs 2007;16:1775-1783.
  250. Raupach T, Hoogsteder PH, Onno van Schayck CP: Nicotine vaccines to assist with smoking cessation: current status of research. Drugs 2012;72:e1-16.
  251. Hartmann-Boyce J, Cahill K, Hatsukami D, Cornuz J: Nicotine vaccines for smoking cessation. Cochrane Database Syst Rev 2012;8:CD007072.
  252. Pentel PR, LeSage MG: New directions in nicotine vaccine design and use. Adv Pharmacol 2014;69:553-580.
  253. Koudelka KJ, Pitek AS, Manchester M, Steinmetz NF: Virus-based nanoparticles as versatile nanomachines. Annu Rev Virol 2015;2:379-401.
  254. Tsvetkova I, Dragnea B: Principles of design of virus nanoparticles for imaging applications; in Khudyakov Y, Pumpens P (eds): Viral Nanotechnology. Boca Raton, CRC Press, 2015, pp 383-390.
    External Resources
  255. Karimi M, Mirshekari H, Moosavi Basri SM, Bahrami S, Moghoofei M, Hamblin MR: Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos. Adv Drug Deliv Rev 2016;106:45-62.
  256. Lee EJ, Lee NK, Kim IS: Bioengineered protein-based nanocage for drug delivery. Adv Drug Deliv Rev 2016;106:157-171.
  257. Wu M, Brown WL, Stockley PG: Cell-specific delivery of bacteriophage-encapsidated ricin A chain. Bioconjug Chem 1995;6:587-595.
  258. Wu M, Brown WL, Hill HR, Stockley PG: Specific cytotoxicity against cells bearing HIV1 gp120 antigen by bacteriophage-encapsidated ricin A chain: implications for cell specific drug delivery. Biochem Soc Trans 1997;25:158S.
  259. Wu M, Brown WL, Hill HR, Stockley PG: Development of a novel drug-delivery system using bacteriophage MS2 capsids. Biochem Soc Trans 1996;24:413S.
  260. Brown WL, Mastico RA, Wu M, Heal KG, Adams CJ, Murray JB, Simpson JC, Lord JM, Taylor-Robinson AW, Stockley PG: RNA bacteriophage capsid-mediated drug delivery and epitope presentation. Intervirology 2002;45:371-380.
  261. Yan R, Hallam A, Stockley PG, Boyes J: Oncogene dependency and the potential of targeted RNAi-based anti-cancer therapy. Biochem J 2014;461:1-13.
  262. Kovacs EW, Hooker JM, Romanini DW, Holder PG, Berry KE, Francis MB: Dual-surface-modified bacteriophage MS2 as an ideal scaffold for a viral capsid-based drug delivery system. Bioconjug Chem 2007;18:1140-1147.
  263. Carrico ZM, Romanini DW, Mehl RA, Francis MB: Oxidative coupling of peptides to a virus capsid containing unnatural amino acids. Chem Commun 2008;10:1205-1207.
  264. Wu W, Hsiao SC, Carrico ZM, Francis MB: Genome-free viral capsids as multivalent carriers for taxol delivery. Angew Chem Int Ed Engl 2009;48:9493-9497.
  265. Tong GJ, Hsiao SC, Carrico ZM, Francis MB: Viral capsid DNA aptamer conjugates as multivalent cell-targeting vehicles. J Am Chem Soc 2009;131:11174-11178.
  266. Stephanopoulos N, Carrico ZM, Francis MB: Nanoscale integration of sensitizing chromophores and porphyrins with bacteriophage MS2. Angew Chem Int Ed Engl 2009;48:9498-9502.
  267. Stephanopoulos N, Tong GJ, Hsiao SC, Francis MB: Dual-surface modified virus capsids for targeted delivery of photodynamic agents to cancer cells. ACS Nano 2010;4:6014-6020.
  268. Ashley CE, Carnes EC, Phillips GK, Durfee PN, Buley MD, Lino CA, Padilla DP, Phillips B, Carter MB, Willman CL, Brinker CJ, Caldeira Jdo C, Chackerian B, Wharton W, Peabody DS: Cell-specific delivery of diverse cargos by bacteriophage MS2 virus-like particles. ACS Nano 2011;5:5729-5745.
  269. Hou B, Saudan P, Ott G, Wheeler ML, Ji M, Kuzmich L, Lee LM, Coffman RL, Bachmann MF, DeFranco AL: Selective utilization of Toll-like receptor and MyD88 signaling in B cells for enhancement of the antiviral germinal center response. Immunity 2011;34:375-384.
  270. Link A, Zabel F, Schnetzler Y, Titz A, Brombacher F, Bachmann MF: Innate immunity mediates follicular transport of particulate but not soluble protein antigen. J Immunol 2012;188:3724-3733.
  271. Anderson EA, Isaacman S, Peabody DS, Wang EY, Canary JW, Kirshenbaum K: Viral nanoparticles donning a paramagnetic coat: conjugation of MRI contrast agents to the MS2 capsid. Nano Lett 2006;6:1160-1164.
  272. Hooker JM, Datta A, Botta M, Raymond KN, Francis MB: Magnetic resonance contrast agents from viral capsid shells: a comparison of exterior and interior cargo strategies. Nano Lett 2007;7:2207-2210.
  273. Hooker JM, O'Neil JP, Romanini DW, Taylor SE, Francis MB: Genome-free viral capsids as carriers for positron emission tomography radiolabels. Mol Imaging Biol 2008;10:182-191.
  274. Pasloske BL, Walkerpeach CR, Obermoeller RD, Winkler M, DuBois DB: Armored RNA technology for production of ribonuclease-resistant viral RNA controls and standards. J Clin Microbiol 1998;36:3590-3594.
    External Resources
  275. Zhang L, Sun Y, Chang L, Jia T, Wang G, Zhang R, Zhang K, Li J: A novel method to produce armored double-stranded DNA by encapsulation of MS2 viral capsids. Appl Microbiol Biotechnol 2015;99:7047-7057.
  276. Wei Y, Yang C, Wei B, Huang J, Wang L, Meng S, Zhang R, Li J: RNase-resistant virus-like particles containing long chimeric RNA sequences produced by two-plasmid coexpression system. J Clin Microbiol 2008;46:1734-1740.
  277. Ponchon L, Catala M, Seijo B, El Khouri M, Dardel F, Nonin-Lecomte S, Tisné C: Co-expression of RNA-protein complexes in Escherichia coli and applications to RNA biology. Nucleic Acids Res 2013;41:e150.
  278. Mikel P, Vasickova P, Kralik P: Methods for preparation of MS2 phage-like particles and their utilization as process control viruses in RT-PCR and qRT-PCR detection of RNA viruses from food matrices and clinical specimens. Food Environ Virol DOI 10.1007/s12560-015-9188-2. Published online: 25 February 2015.
  279. Frietze K, Peabody D, Chackerian B: Engineering virus-like particles as vaccine platforms. Curr Opin Virol 2016;18:44-49.
  280. Saboo S, Tumban E, Peabody J, Wafula D, Peabody DS, Chackerian B, Muttil P: An optimized formulation of a thermostable spray-dried virus-like particles vaccine against human papillomavirus. Mol Pharm 2016;13:1646-1655.
  281. Prel A, Caval V, Gayon R, Ravassard P, Duthoit C, Payen E, Maouche-Chretien L, Creneguy A, Nguyen TH, Martin N, Piver E, Sevrain R, Lamouroux L, Leboulch P, Deschaseaux F, Bouillé P, Sensébé L, Pagès JC: Highly efficient in vitro and in vivo delivery of functional RNAs using new versatile MS2-chimeric retrovirus-like particles. Mol Ther Methods Clin Dev 2015;2:15039.
  282. Frietze KM, Roden RB, Lee JH, Shi Y, Peabody DS, Chackerian B: Identification of anti-CA125 antibody responses in ovarian cancer patients by a novel deep sequence-coupled biopanning platform. Cancer Immunol Res 2016;4:157-164.
  283. Witus LS, Francis MB: Using synthetically modified proteins to make new materials. Acc Chem Res 2011;44:774-783.
  284. Stephanopoulos N, Liu M, Tong GJ, Li Z, Liu Y, Yan H, Francis MB: Immobilization and one-dimensional arrangement of virus capsids with nanoscale precision using DNA origami. Nano Lett 2010;10:2714-2720.
  285. Wang D, Capehart SL, Pal S, Liu M, Zhang L, Schuck PJ, Liu Y, Yan H, Francis MB, De Yoreo JJ: Hierarchical assembly of plasmonic nanostructures using virus capsid scaffolds on DNA origami templates. ACS Nano 2014;8:7896-7904.
  286. Friedman SD, Genthner FJ, Gentry J, Sobsey MD, Vinjé J: Gene mapping and phylogenetic analysis of the complete genome from 30 single-stranded RNA male-specific coliphages (family Leviviridae). J Virol 2009;83:11233-11243.
  287. Rumnieks J, Tars K: Diversity of pili-specific bacteriophages: genome sequence of IncM plasmid-dependent RNA phage M. BMC Microbiol 2012;12:277.
  288. Kannoly S, Shao Y, Wang IN: Rethinking the evolution of single-stranded RNA (ssRNA) bacteriophages based on genomic sequences and characterizations of two R-plasmid-dependent ssRNA phages, C-1 and Hgal1. J Bacteriol 2012;194:5073-5079.
  289. Friedman SD, Snellgrove WC, Genthner FJ: Genomic sequences of two novel levivirus single-stranded RNA coliphages (family Leviviridae): evidence for recombination in environmental strains. Viruses 2012;4:1548-1568.
  290. Vinjé J, Oudejans SJ, Stewart JR, Sobsey MD, Long SC: Molecular detection and genotyping of male-specific coliphages by reverse transcription-PCR and reverse line blot hybridization. Appl Environ Microbiol 2004;70:5996-6004.
  291. Greninger AL, DeRisi JL: Draft genome sequences of Leviviridae RNA phages EC and MB recovered from San Francisco wastewater. Genome Announc 2015;3:e00652-15.
  292. Krishnamurthy SR, Janowski AB, Zhao G, Barouch D, Wang D: Hyperexpansion of RNA bacteriophage diversity. PLoS Biol 2016;14:e1002409.
  293. Dykeman EC, Stockley PG, Twarock R: Solving a Levinthal's paradox for virus assembly identifies a unique antiviral strategy. Proc Natl Acad Sci USA 2014;111:5361-5366.
  294. Dika C, Duval JF, Ly-Chatain HM, Merlin C, Gantzer C: Impact of internal RNA on aggregation and electrokinetics of viruses: comparison between MS2 phage and corresponding virus-like particles. Appl Environ Microbiol 2011;77:4939-4948.
  295. Schmitz N, Beerli RR, Bauer M, Jegerlehner A, Dietmeier K, Maudrich M, Pumpens P, Saudan P, Bachmann MF: Universal vaccine against influenza virus: Linking TLR signaling to anti-viral protection. Eur J Immunol 2012;42:863-869.
  296. Crossey E, Amar MJ, Sampson M, Peabody J, Schiller JT, Chackerian B, Remaley AT: A cholesterol-lowering VLP vaccine that targets PCSK9. Vaccine 2015;33:5747-5755.
  297. Dong YM, Zhang GG, Huang XJ, Chen L, Chen HT: Promising MS2 mediated virus-like particle vaccine against foot-and-mouth disease. Antiviral Res 2015;117:39-43.
  298. Stockley PG, Mastico RA: Use of fusions to viral coat proteins as antigenic carriers for vaccine development. Methods Enzymol 2000;326:551-569.
  299. Lagoutte P, Mignon C, Donnat S, Stadthagen G, Mast J, Sodoyer R, Lugari A, Werle B: Scalable chromatography-based purification of virus-like particle carrier for epitope based influenza A vaccine produced in Escherichia coli. J Virol Methods 2016;232:8-11.
  300. Caldeira J, Bustos J, Peabody J, Chackerian B, Peabody DS: Epitope-specific anti-hCG vaccines on a virus like particle platform. PLoS One 2015;10:e0141407.
  301. Pastori C, Tudor D, Diomede L, Drillet AS, Jegerlehner A, Röhn TA, Bomsel M, Lopalco L: Virus like particle based strategy to elicit HIV-protective antibodies to the alpha-helic regions of gp41. Virology 2012;431:1-11.
  302. Freer G, Giannecchini S, Tissot A, Bachmann MF, Rovero P, Serres PF, Bendinelli M: Dissection of seroreactivity against the tryptophan-rich motif of the feline immunodeficiency virus transmembrane glycoprotein. Virology 2004;322:360-369.
  303. Huber A, Bachmann M, Jennings G, Tissot A, Langedijk J, Timmerman P, Slootstra J, Boshuizen R: Circular CCR5 peptide conjugates and uses thereof. WIPO Patent Application WO/2008/074895. June 26, 2008.
  304. Sommerfelt MA: Circular CCR5 peptide conjugates and uses thereof (WO2008074895). Expert Opin Ther Pat 2009;19:1323-1328.
  305. Hunter Z, Smyth HD, Durfee P, Chackerian B: Induction of mucosal and systemic antibody responses against the HIV coreceptor CCR5 upon intramuscular immunization and aerosol delivery of a virus-like particle based vaccine. Vaccine 2009;28:403-414.
  306. van Rompay KK, Hunter Z, Jayashankar K, Peabody J, Montefiori D, Labranche CC, Keele BF, Jensen K, Abel K, Chackerian B: A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge with simian immunodeficiency virus SIVmac251. J Virol 2014;88:2011-2024.
  307. Kündig TM, Senti G, Schnetzler G, Wolf C, Prinz Vavricka BM, Fulurija A, Hennecke F, Sladko K, Jennings GT, Bachmann MF: Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults. J Allergy Clin Immunol 2006;117:1470-1476.
  308. Schmitz N, Dietmeier K, Bauer M, Maudrich M, Utzinger S, Muntwiler S, Saudan P, Bachmann MF: Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy. J Exp Med 2009;206:1941-1955.
  309. Akache B, Weeratna RD, Deora A, Thorn JM, Champion B, Merson JR, Davis HL, McCluskie MJ: Anti-IgE Qβ-VLP conjugate vaccine self-adjuvants through activation of TLR7. Vaccines (Basel) 2016;4:3.
  310. Araujo RN, Franco PF, Rodrigues H, Santos LC, McKay CS, Sanhueza CA, Brito CR, Azevedo MA, Venuto AP, Cowan PJ, Almeida IC, Finn MG, Marques AF: Amblyomma sculptum tick saliva: α-Gal identification, antibody response and possible association with red meat allergy in Brazil. Int J Parasitol 2016;46:213-220.
  311. Chackerian B, Rangel M, Hunter Z, Peabody DS: Virus and virus-like particle-based immunogens for Alzheimer's disease induce antibody responses against amyloid-β without concomitant T cell responses. Vaccine 2006;24:6321-6331.
  312. Li QY, Gordon MN, Chackerian B, Alamed J, Ugen KE, Morgan D: Virus-like peptide vaccines against Aβ N-terminal or C-terminal domains reduce amyloid deposition in APP transgenic mice without addition of adjuvant. J Neuroimmune Pharmacol 2010;5:133-142.
  313. Wiessner C, Wiederhold KH, Tissot AC, Frey P, Danner S, Jacobson LH, Jennings GT, Lüönd R, Ortmann R, Reichwald J, Zurini M, Mir A, Bachmann MF, Staufenbiel M: The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. J Neurosci 2011;31:9323-9331.
  314. Tissot AC, Spohn G, Jennings GT, Shamshiev A, Kurrer MO, Windak R, Meier M, Viesti M, Hersberger M, Kündig TM, Ricci R, Bachmann MF: A VLP-based vaccine against interleukin-1α protects mice from atherosclerosis. Eur J Immunol 2013;43:716-722.
  315. Spohn G, Keller I, Beck M, Grest P, Jennings GT, Bachmann MF: Active immunization with IL-1 displayed on virus-like particles protects from autoimmune arthritis. Eur J Immunol 2008;38:877-887.
  316. Guler R, Parihar SP, Spohn G, Johansen P, Brombacher F, Bachmann MF: Blocking IL-1α but not IL-1β increases susceptibility to chronic Mycobacterium tuberculosis infection in mice. Vaccine 2011;29:1339-1346.
  317. Röhn TA, Jennings GT, Hernandez M, Grest P, Beck M, Zou Y, Kopf M, Bachmann MF: Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis. Eur J Immunol 2006;36:2857-2867.
  318. Sonderegger I, Röhn TA, Kurrer MO, Iezzi G, Zou Y, Kastelein RA, Bachmann MF, Kopf M: Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis. Eur J Immunol 2006;36:2849-2856.
  319. Dallenbach K, Maurer P, Röhn T, Zabel F, Kopf M, Bachmann MF: Protective effect of a germline, IL-17-neutralizing antibody in murine models of autoimmune inflammatory disease. Eur J Immunol 2015;45:1238-1247.
  320. Spohn G, Guler R, Johansen P, Keller I, Jacobs M, Beck M, Rohner F, Bauer M, Dietmeier K, Kündig TM, Jennings GT, Brombacher F, Bachmann MF: A virus-like particle-based vaccine selectively targeting soluble TNF-α protects from arthritis without inducing reactivation of latent tuberculosis. J Immunol 2007;178:7450-7457.
  321. Spohn G, Schori C, Keller I, Sladko K, Sina C, Guler R, Schwarz K, Johansen P, Jennings GT, Bachmann MF: Preclinical efficacy and safety of an anti-IL-1β vaccine for the treatment of type 2 diabetes. Mol Ther Methods Clin Dev 2014;1:14048.
  322. Cavelti-Weder C, Timper K, Seelig E, Keller C, Osranek M, Lässing U, Spohn G, Maurer P, Müller P, Jennings GT, Willers J, Saudan P, Donath MY, Bachmann MF: Development of an interleukin-1β vaccine in patients with type 2 diabetes. Mol Ther 2016;24:1003-1012.
  323. Zou Y, Sonderegger I, Lipowsky G, Jennings GT, Schmitz N, Landi M, Kopf M, Bachmann MF: Combined vaccination against IL-5 and eotaxin blocks eosinophilia in mice. Vaccine 2010;28:3192-3200.
  324. Chackerian B, Durfee MR, Schiller JT: Virus-like display of a neo-self antigen reverses B cell anergy in a B cell receptor transgenic mouse model. J Immunol 2008;180:5816-5825.
  325. Ambühl PM, Tissot AC, Fulurija A, Maurer P, Nussberger J, Sabat R, Nief V, Schellekens C, Sladko K, Roubicek K, Pfister T, Rettenbacher M, Volk HD, Wagner F, Müller P, Jennings GT, Bachmann MF: A vaccine for hypertension based on virus-like particles: preclinical efficacy and phase I safety and immunogenicity. J Hypertens 2007;25:63-72.
  326. Tissot AC, Maurer P, Nussberger J, Sabat R, Pfister T, Ignatenko S, Volk HD, Stocker H, Müller P, Jennings GT, Wagner F, Bachmann MF: Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. Lancet 2008;371:821-827.
  327. Chen X, Qiu Z, Yang S, Ding D, Chen F, Zhou Y, Wang M, Lin J, Yu X, Zhou Z, Liao Y: Effectiveness and safety of a therapeutic vaccine against angiotensin II receptor type 1 in hypertensive animals. Hypertension 2013;61:408-416.
  328. Ding D, Du Y, Qiu Z, Yan S, Chen F, Wang M, Yang S, Zhou Y, Hu X, Deng Y, Wang S, Wang L, Zhang H, Wu H, Yu X, Zhou Z, Liao Y, Chen X: Vaccination against type 1 angiotensin receptor prevents streptozotocin-induced diabetic nephropathy. J Mol Med 2016;94:207-218.
  329. Zhou Y, Wang S, Qiu Z, Song X, Pan Y, Hu X, Zhang H, Deng Y, Ding D, Wu H, Yang S, Wang M, Zhou Z, Liao Y, Chen X: ATRQβ-001 vaccine prevents atherosclerosis in apolipoprotein E-null mice. J Hypertens 2016;34:474-485.
  330. Röhn TA, Ralvenius WT, Paul J, Borter P, Hernandez M, Witschi R, Grest P, Zeilhofer HU, Bachmann MF, Jennings GT: A virus-like particle-based anti-nerve growth factor vaccine reduces inflammatory hyperalgesia: potential long-term therapy for chronic pain. J Immunol 2011;186:1769-1780.
  331. Skibinski DA, Hanson BJ, Lin Y, von Messling V, Jegerlehner A, Tee JB, Chye de H, Wong SK, Ng AA, Lee HY, Au B, Lee BT, Santoso L, Poidinger M, Fairhurst AM, Matter A, Bachmann MF, Saudan P, Connolly JE: Enhanced neutralizing antibody titers and Th1 polarization from a novel Escherichia coli derived pandemic influenza vaccine. PLoS One 2013;8:e76571.
  332. Jegerlehner A, Zabel F, Langer A, Dietmeier K, Jennings GT, Saudan P, Bachmann MF: Bacterially produced recombinant influenza vaccines based on virus-like particles. PLoS One 2013;8:e78947.
  333. Low JG, Lee LS, Ooi EE, Ethirajulu K, Yeo P, Matter A, Connolly JE, Skibinski DA, Saudan P, Bachmann M, Hanson BJ, Lu Q, Maurer-Stroh S, Lim S, Novotny-Diermayr V: Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine: results from a double-blinded, randomized phase I clinical trial in healthy Asian volunteers. Vaccine 2014;32:5041-5048.
  334. Khan F, Porter M, Schwenk R, DeBot M, Saudan P, Dutta S: Head-to-head comparison of soluble vs. Qβ VLP circumsporozoite protein vaccines reveals selective enhancement of NANP repeat responses. PLoS One 2015;10:e0142035.
  335. Speiser DE, Schwarz K, Baumgaertner P, Manolova V, Devevre E, Sterry W, Walden P, Zippelius A, Conzett KB, Senti G, Voelter V, Cerottini JP, Guggisberg D, Willers J, Geldhof C, Romero P, Kündig T, Knuth A, Dummer R, Trefzer U, Bachmann MF: Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients. J Immunother 2010;33:848-858.
  336. Braun M, Jandus C, Maurer P, Hammann-Haenni A, Schwarz K, Bachmann MF, Speiser DE, Romero P: Virus-like particles induce robust human T-helper cell responses. Eur J Immunol 2012;42:330-340.
  337. Goldinger SM, Dummer R, Baumgaertner P, Mihic-Probst D, Schwarz K, Hammann-Haenni A, Willers J, Geldhof C, Prior JO, Kündig TM, Michielin O, Bachmann MF, Speiser DE: Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8-T-cell responses in melanoma patients. Eur J Immunol 2012;42:3049-3061.
  338. McCluskie MJ, Thorn J, Gervais DP, Stead DR, Zhang N, Benoit M, Cartier J, Kim IJ, Bhattacharya K, Finneman JI, Merson JR, Davis HL: Anti-nicotine vaccines: comparison of adjuvanted CRM197 and Qβ-VLP conjugate formulations for immunogenicity and function in non-human primates. Int Immunopharmacol 2015;29:663-671.
  339. Fulurija A, Lutz TA, Sladko K, Osto M, Wielinga PY, Bachmann MF, Saudan P: Vaccination against GIP for the treatment of obesity. PLoS One 2008;3:e3163.
  340. Spohn G, Schwarz K, Maurer P, Illges H, Rajasekaran N, Choi Y, Jennings GT, Bachmann MF: Protection against osteoporosis by active immunization with TRANCE/RANKL displayed on virus-like particles. J Immunol 2005;175:6211-6218.
  341. Kalniņš G, Cielēns I, Renhofa R: Virus-like particles addressed by HBV preS1 sequences. Environ Exp Biol 2013;11:1-8.
  342. Rūmnieks J, Freivalds J, Cielēns I, Renhofa R: Specificity of packaging mRNAs in bacteriophage GA virus-like particles in yeast Saccharomyces cerevisiae. Acta Universitatis Latviensis Biol 2008;745:145-154.
  343. Strods A, Ārgule D, Cielēns I, Jackeviča L, Renhofa R: Expression of GA coat protein-derived mosaic virus-like particles in Saccharomyces cerevisiae and packaging in vivo of mRNAs into particles. Proc Latv Acad Sci 2012;66:234-241.
    External Resources
  344. Ārgule D, Cielēns I, Renhofa R, Strods A: In vivo packaging of yeast-produced bacteriophage GA derived virus-like particles. Proc Latv Acad Sci 2016, in press.
  345. Wu M, Sherwin T, Brown WL, Stockley PG: Delivery of antisense oligonucleotides to leukemia cells by RNA bacteriophage capsids. Nanomedicine 2005;1:67-76.
  346. Wei B, Wei Y, Zhang K, Wang J, Xu R, Zhan S, Lin G, Wang W, Liu M, Wang L, Zhang R, Li J: Development of an antisense RNA delivery system using conjugates of the MS2 bacteriophage capsids and HIV-1 TAT cell-penetrating peptide. Biomed Pharmacother 2009;63:313-318.
  347. Pan Y, Zhang Y, Jia T, Zhang K, Li J, Wang L: Development of a microRNA delivery system based on bacteriophage MS2 virus-like particles. FEBS J 2012;279:1198-1208.
  348. Pan Y, Jia T, Zhang Y, Zhang K, Zhang R, Li J, Wang L: MS2 VLP-based delivery of microRNA-146a inhibits autoantibody production in lupus-prone mice. Int J Nanomedicine 2012;7:5957-5967.
  349. Yao Y, Jia T, Pan Y, Gou H, Li Y, Sun Y, Zhang R, Zhang K, Lin G, Xie J, Li J, Wang L: Using a novel microRNA delivery system to inhibit osteoclastogenesis. Int J Mol Sci 2015;16:8337-8350.
  350. Galaway FA, Stockley PG: MS2 viruslike particles: a robust, semisynthetic targeted drug delivery platform. Mol Pharm 2013;10:59-68.
  351. Capehart SL, Coyle MP, Glasgow JE, Francis MB: Controlled integration of gold nanoparticles and organic fluorophores using synthetically modified MS2 viral capsids. J Am Chem Soc 2013;135:3011-3016.
  352. Cohen BA, Bergkvist M: Targeted in vitro photodynamic therapy via aptamer-labeled, porphyrin-loaded virus capsids. J Photochem Photobiol B 2013;121:67-74.
  353. ElSohly AM, Netirojjanakul C, Aanei IL, Jager A, Bendall SC, Farkas ME, Nolan GP, Francis MB: Synthetically modified viral capsids as versatile carriers for use in antibody-based cell targeting. Bioconjug Chem 2015;26:1590-1596.
  354. Chang L, Wang G, Jia T, Zhang L, Li Y, Han Y, Zhang K, Lin G, Zhang R, Li J, Wang L: Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma. Oncotarget 2016;7:23988-24004.
  355. Sun S, Li W, Sun Y, Pan Y, Li J: A new RNA vaccine platform based on MS2 virus-like particles produced in Saccharomyces cerevisiae. Biochem Biophys Res Commun 2011;407:124-128.
  356. Glasgow JE, Capehart SL, Francis MB, Tullman-Ercek D: Osmolyte-mediated encapsulation of proteins inside MS2 viral capsids. ACS Nano 2012;6:8658-8664.
  357. Li J, Sun Y, Jia T, Zhang R, Zhang K, Wang L: Messenger RNA vaccine based on recombinant MS2 virus-like particles against prostate cancer. Int J Cancer 2014;134:1683-1694.
  358. Steinmetz NF, Hong V, Spoerke ED, Lu P, Breitenkamp K, Finn MG, Manchester M: Buckyballs meet viral nanoparticles: candidates for biomedicine. J Am Chem Soc 2009;131:17093-17095.
  359. Rhee JK, Hovlid M, Fiedler JD, Brown SD, Manzenrieder F, Kitagishi H, Nycholat C, Paulson JC, Finn MG: Colorful virus-like particles: fluorescent protein packaging by the Qβ capsid. Biomacromolecules 2011;12:3977-3981.
  360. Rhee JK, Baksh M, Nycholat C, Paulson JC, Kitagishi H, Finn MG: Glycan-targeted virus-like nanoparticles for photodynamic therapy. Biomacromolecules 2012;13:2333-2338.
  361. Lau JL, Baksh MM, Fiedler JD, Brown SD, Kussrow A, Bornhop DJ, Ordoukhanian P, Finn MG: Evolution and protein packaging of small-molecule RNA aptamers. ACS Nano 2011;5:7722-7729.
  362. Wu Z, Tang LJ, Zhang XB, Jiang JH, Tan W: Aptamer-modified nanodrug delivery systems. ACS Nano 2011;5:7696-7699.
  363. Hovlid ML, Lau JL, Breitenkamp K, Higginson CJ, Laufer B, Manchester M, Finn MG: Encapsidated atom-transfer radical polymerization in Qβ virus-like nanoparticles. ACS Nano 2014;8:8003-8014.
  364. Fiedler JD, Brown SD, Lau JL, Finn MG: RNA-directed packaging of enzymes within virus-like particles. Angew Chem Int Ed Engl 2010;49:9648-9651.
  365. Hong V, Udit AK, Evans RA, Finn MG: Electrochemically protected copper(I)-catalyzed azide-alkyne cycloaddition. Chembiochem 2008;9:1481-1486.
  366. Kaltgrad E, O'Reilly MK, Liao L, Han S, Paulson JC, Finn MG: On-virus construction of polyvalent glycan ligands for cell-surface receptors. J Am Chem Soc 2008;130:4578-4579.
  367. Kussrow A, Kaltgrad E, Wolfenden ML, Cloninger MJ, Finn MG, Bornhop DJ: Measurement of monovalent and polyvalent carbohydrate-lectin binding by back-scattering interferometry. Anal Chem 2009;81:4889-4897.
  368. Udit AK, Everett C, Gale AJ, Reiber Kyle J, Ozkan M, Finn MG: Heparin antagonism by polyvalent display of cationic motifs on virus-like particles. Chembiochem 2009;10:503-510.
  369. Gale AJ, Elias DJ, Averell PM, Teirstein PS, Buck M, Brown SD, Polonskaya Z, Udit AK, Finn MG: Engineered virus-like nanoparticles reverse heparin anticoagulation more consistently than protamine in plasma from heparin-treated patients. Thromb Res 2011;128:e9-13.
  370. Udit AK: Engineered virus-like nanoparticle heparin antagonists. Conf Proc IEEE Eng Med Biol Soc 2013;2013:4118-4120.
  371. Brown SD, Fiedler JD, Finn MG: Assembly of hybrid bacteriophage Qβ virus-like particles. Biochemistry 2009;48:11155-11157.
  372. Astronomo RD, Kaltgrad E, Udit AK, Wang SK, Doores KJ, Huang CY, Pantophlet R, Paulson JC, Wong CH, Finn MG, Burton DR: Defining criteria for oligomannose immunogens for HIV using icosahedral virus capsid scaffolds. Chem Biol 2010;17:357-370.
  373. Banerjee D, Liu AP, Voss NR, Schmid SL, Finn MG: Multivalent display and receptor-mediated endocytosis of transferrin on virus-like particles. Chembiochem 2010;11:1273-1279.
  374. Cigler P, Lytton-Jean AK, Anderson DG, Finn MG, Park SY: DNA-controlled assembly of a NaTl lattice structure from gold nanoparticles and protein nanoparticles. Nat Mater 2010;9:918-922.
  375. Manzenrieder F, Luxenhofer R, Retzlaff M, Jordan R, Finn MG: Stabilization of virus-like particles with poly(2-oxazoline)s. Angew Chem Int Ed Engl 2011;50:2601-2605.
  376. Pokorski JK, Breitenkamp K, Liepold LO, Qazi S, Finn MG: Functional virus-based polymer-protein nanoparticles by atom transfer radical polymerization. J Am Chem Soc 2011;133:9242-9245.
  377. Pokorski JK, Hovlid ML, Finn MG: Cell targeting with hybrid Qβ virus-like particles displaying epidermal growth factor. Chembiochem 2011;12:2441-2447.
  378. Mead G, Hiley M, Ng T, Fihn C, Hong K, Groner M, Miner W, Drugan D, Hollingsworth W, Udit AK: Directed polyvalent display of sulfated ligands on virus nanoparticles elicits heparin-like anticoagulant activity. Bioconjug Chem 2014;25:1444-1452.
  379. Groner M, Ng T, Wang W, Udit AK: Bio-layer interferometry of a multivalent sulfated virus nanoparticle with heparin-like anticoagulant activity. Anal Bioanal Chem 2015;407:5843-5847.
  380. Isarov SA, Lee PW, Pokorski JK: ‘Graft-to' protein/polymer conjugates using polynorbornene block copolymers. Biomacromolecules 2016;17:641-648.
  381. Kang JS, Yoon JH: Dynamics of RNA bacteriophage MS2 observed with a long-lifetime metal-ligand complex. J Photosci 2004;11:35-40.
  382. Datta A, Hooker JM, Botta M, Francis MB, Aime S, Raymond KN: High relaxivity gadolinium hydroxypyridonate-viral capsid conjugates: nanosized MRI contrast agents. J Am Chem Soc 2008;130:2546-2552.
  383. Meldrum T, Seim KL, Bajaj VS, Palaniappan KK, Wu W, Francis MB, Wemmer DE, Pines A: A xenon-based molecular sensor assembled on an MS2 viral capsid scaffold. J Am Chem Soc 2010;132:5936-5937.
  384. Farkas ME, Aanei IL, Behrens CR, Tong GJ, Murphy ST, O'Neil JP, Francis MB: PET imaging and biodistribution of chemically modified bacteriophage MS2. Mol Pharm 2013;10:69-76.
  385. Obermeyer AC, Capehart SL, Jarman JB, Francis MB: Multivalent viral capsids with internal cargo for fibrin imaging. PLoS One 2014;9:e100678.
  386. Elena CM, Leticia F, Emilia T, Patricia E, Mariella T: Evaluation of a labelled bacteriophage with 99mTc as a potential agent for infection diagnosis. Curr Radiopharm 2016;9:137-142.
  387. Prasuhn DE Jr, Singh P, Strable E, Brown S, Manchester M, Finn MG: Plasma clearance of bacteriophage Qβ particles as a function of surface charge. J Am Chem Soc 2008;130:1328-1334.
  388. Kim MS, Kim JH, Son BW, Kang JS: Dynamics of bacteriophage R17 probed with a long-lifetime Ru(II) metal-ligand complex. J Fluoresc 2010;20:713-718.
  389. Carrillo-Tripp M, Shepherd CM, Borelli IA, Venkataraman S, Lander G, Natarajan P, Johnson JE, Brooks CL 3rd, Reddy VS: VIPERdb2: an enhanced and web API enabled relational database for structural virology. Nucleic Acids Res 2009;37:D436-D442.
  390. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE: UCSF Chimera - a visualization system for exploratory research and analysis. J Comput Chem 2004;25:1605-1612.
ppt logo Download Images (.pptx)


Figures
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail

Tables
Thumbnail
Thumbnail
Thumbnail
Thumbnail