Viruses and their uses in nanotechnology

Singh, Pratik; Gonzalez, Maria J.; Manchester, Marianne

doi:10.1002/ddr.20064

Cited by 168 publications

(152 citation statements)

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“…A variety of nanoparticles including VNPs are being developed for biomedical applications [1,8,9,34,52], however little information is available about the biological behavior of these particles in vivo. Such studies are important for the design and development of a successful bio-nanoparticle.…”

Section: Discussionmentioning

confidence: 99%

“…Being primarily protein-based, they have a natural biocompatibility, particularly viruses that do not cause human disease such as plant viruses or bacteriophages. Virus capsids are relatively rigid structures, making it feasible to display molecules or epitopes in precise spatial distributions at the nanoscale, a difficult task using inorganic or lipid materials [15,52]. Viral nanoparticles (VNPs) currently in development include cowpea mosaic virus (CPMV) [9,29,51,[58][59][60], cowpea chlorotic mottle virus (CCMV) [2], bacteriophages (MS2 [3,8,23,43], M13 [28,31,32] Qβ [4]) and polyoma virus [1].…”

Section: Introductionmentioning

confidence: 99%

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Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

Singh

Prasuhn

Yeh

et al. 2007

Journal of Controlled Release

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231

224

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Virus-based nanoparticles (VNPs) from a variety of sources are being developed for biomedical and nanotechnology applications that include tissue targeting and drug delivery. However, the fate of most of those particles in vivo has not been investigated. Cowpea mosaic virus (CPMV), a plant comovirus, has been found to be amenable to the attachment of a variety of molecules to its coat protein, as well as to modification of the coat protein sequence by genetic means. We report here the results of studies of the bio-distribution, toxicology, and pathology of CPMV in mice. Plasma clearance and tissue biodistribution were measured using CPMV particles derivatized with lanthanide metal complexes. CPMV particles were cleared rapidly from plasma, falling to undetectable levels within 20 minutes. By 30 minutes the majority of the injected VNPs were trapped in the liver and to a lesser extent the spleen with undetectable amounts in other tissues. At doses of 1 mg, 10 mg and 100 mg per kg body weight, no toxicity was noted and the mice appeared to be normal. Hematology was essentially normal, although with the highest dose examined, the mice were somewhat leukopenic with relative decreases in both neutrophils and lymphocytes. Histological examination of spleen showed cellular infiltration, which upon flow cytometry analyses revealed elevated B lymphocytes on the first day following virus administration that subsequently subsided. Microscopic evaluation of various other tissues revealed a lack of apparent tissue degeneration or necrosis. Overall, CPMV appears to be a safe and non-toxic platform for in vivo biomedical applications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

Singh

Prasuhn

Yeh

et al. 2007

Journal of Controlled Release

Self Cite

231

224

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“…For the development of new antiviral drugs, further insight into the replication cycle and assembly pathway of the virus is needed (2). Moreover, there is a growing interest in HBV and other viral particles as vehicles for drug delivery and as platforms for nanoparticle technology (3). In this context, precise biophysical characterization of these particles represents essential basic information.…”

Section: H Epatitis B Virus (Hbv) Is a Major Cause Of Liver Disease Inmentioning

confidence: 99%

High-resolution mass spectrometry of viral assemblies: Molecular composition and stability of dimorphic hepatitis B virus capsids

Uetrecht

Versluis

Watts

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

201

206

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Hepatitis B virus (HBV) is a major human pathogen. In addition to its importance in human health, there is growing interest in adapting HBV and other viruses for drug delivery and other nanotechnological applications. In both contexts, precise biophysical characterization of these large macromolecular particles is fundamental. HBV capsids are unusual in that they exhibit two distinct icosahedral geometries, nominally composed of 90 and 120 dimers with masses of Ϸ3 and Ϸ4 MDa, respectively. Here, a mass spectrometric approach was used to determine the masses of both capsids to within 0.1%. It follows that both lattices are complete, consisting of exactly 180 and 240 subunits. Nanoindentation experiments by atomic-force microscopy indicate that both capsids have similar stabilities. The data yielded a Young's modulus of Ϸ0.4 GPa. This experimental approach, anchored on very precise and accurate mass measurements, appears to hold considerable potential for elucidating the assembly of viruses and other macromolecular particles.atomic force microscopy ͉ collision-induced dissociation ͉ macromolecular mass spectrometry ͉ virus assembly ͉ viral structural biology H epatitis B virus (HBV) is a major cause of liver disease in humans (1), with Ͼ350 million people suffering from chronic infection. For the development of new antiviral drugs, further insight into the replication cycle and assembly pathway of the virus is needed (2). Moreover, there is a growing interest in HBV and other viral particles as vehicles for drug delivery and as platforms for nanoparticle technology (3). In this context, precise biophysical characterization of these particles represents essential basic information.HBV has an enveloped virion. Single-stranded viral RNA is packaged into the assembling capsid and, within this compartment, is reverse-transcribed into DNA (4, 5). The DNAcontaining nucleocapsid then proceeds to envelopment. Both in vivo and in vitro, the capsid protein (cp) forms icosahedral capsids of two sizes, corresponding to triangulation numbers of T ϭ 3 and T ϭ 4 (6), nominally consisting of 180 and 240 subunits, respectively (7-10). Cp has a 140-residue N-terminal core domain connected to a 34-residue ''protamine domain'' by a 10-residue linker (11). The protamine domain binds RNA, whereas the core domain is necessary and sufficient for capsid assembly. The ratio of T ϭ 3 to T ϭ 4 capsids produced depends on the length of the linker and the conditions of assembly: The smaller T ϭ 3 capsid becomes progressively more abundant as the linker is shortened (12). The building-block for capsid formation is a dimer stabilized via an intermolecular four-helix bundle (13-15) and a disulfide bond within the bundle (Cys61). However, dimerization and assembly also occur in the absence of the disulfide, e.g., when Cys61 is replaced with Ala (10, 12). The capsid has protruding spikes at the dimer interfaces that display most of the antigenic epitopes and holes at the symmetry axes that allow infusion of nucleotides for reverse transcription (7, ...

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“…1 VNPs are defined here as viral particles that carry nongenomic cargo and can bind and enter a new host cell to deliver the cargo. VNPs are frequently derived from plant viruses or bacteriophages.…”

Section: ■ Introductionmentioning

confidence: 99%

The Packaging of Different Cargo into Enveloped Viral Nanoparticles

Fan

Tsvetkova²,

Khuong³

et al. 2012

Mol. Pharmaceutics

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Viral nanoparticles used for biomedical applications must be able to discriminate between tumor or virus-infected host cells and healthy host cells. In addition, viral nanoparticles must have the flexibility to incorporate a wide range of cargo, from inorganic metals to mRNAs to small molecules. Alphaviruses are a family of enveloped viruses for which some species are intrinsically capable of systemic tumor targeting. Alphavirus virus-like particles, or viral nanoparticles, can be generated from in vitro self-assembled core-like particles using nonviral nucleic acid. In this work, we expand on the types of cargo that can be incorporated into alphavirus core-like particles and the molecular requirements for packaging this cargo. We demonstrate that different core-like particle templates can be further enveloped to form viral nanoparticles that are capable of cell entry. We propose that alphaviruses can be selectively modified to create viral nanoparticles for biomedical applications and basic research.

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Viruses and their uses in nanotechnology

Cited by 168 publications

References 168 publications

Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

High-resolution mass spectrometry of viral assemblies: Molecular composition and stability of dimorphic hepatitis B virus capsids

The Packaging of Different Cargo into Enveloped Viral Nanoparticles

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