Human JC virus-like particles as a gene delivery vector

Chang, Chien‐Wen; Wang, Meilin; Ou, Wei-Chih; Chen, Pei-Lain; Shen, Cheng‐Huang; Lin, Paul Y.; Fang, Chiung‐Yao; Chang, Deching

doi:10.1517/14712598.2011.583914

Cited by 26 publications

(19 citation statements)

References 68 publications

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“…The utilization of polyoma JC based VLPs has previously been reported for gene transfer in tissue culture and cell lines 18,19 and was shown to be an efficient method for the transduction of in vitro packaged DNA. Also, the delivery of encapsulated small molecules was demonstrated with propidium iodide as an example of pharmaceutical substances.…”

Section: Discussionmentioning

confidence: 99%

“…18,19 Cellular entry is mediated through binding and internalization of glycolipids and sialoglycoproteins, including LSTc-binding, and by interaction with the specific serotonin receptor, 5-hydroxytryptamine-receptor 2a. 20,21,22 The effective transfer of genetic material in virus-like particles (VLPs) has been reported using a recombinant VP1 protein generated in Escherichia coli bacteria.…”

Section: Introductionmentioning

confidence: 99%

“…20,21,22 The effective transfer of genetic material in virus-like particles (VLPs) has been reported using a recombinant VP1 protein generated in Escherichia coli bacteria. 8,19 …”

Section: Introductionmentioning

confidence: 99%

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In Vivo siRNA Delivery Using JC Virus-like Particles Decreases the Expression of RANKL in Rats

Hoffmann

Böker

Schneider

et al. 2016

Molecular Therapy - Nucleic Acids

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Bone remodeling requires a precise balance between formation and resorption. This complex process involves numerous factors that orchestrate a multitude of biochemical events. Among these factors are hormones, growth factors, vitamins, cytokines, and, most notably, osteoprotegerin (OPG) and the receptor activator for nuclear factor-kappaB ligand (RANKL). Inflammatory cytokines play a major role in shifting the RANKL/OPG balance toward excessive RANKL, resulting in osteoclastogenesis, which in turn initiates bone resorption, which is frequently associated with osteoporosis. Rebalancing RANKL/OPG levels may be achieved through either upregulation of OPG or through transient silencing of RANKL by means of RNA interference. Here, we describe the utilization of a viral capsid-based delivery system for in vivo and in vitro RNAi using synthetic small interfering RNA (siRNA) molecules in rat osteoblasts. Polyoma JC virus-derived virus-like particles are capable of delivering siRNAs to target RANKL in osteoblast cells both in vitro and in a rat in vivo system. Expression levels were monitored using quantitative real-time polymerase reaction and enzyme-linked immunosorbent assay after single and repeated injections over a 14-day period. Our data indicate that this is an efficient and safe route for in vivo delivery of gene modulatory tools to study important molecular factors in a rat osteoporosis model.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Vivo siRNA Delivery Using JC Virus-like Particles Decreases the Expression of RANKL in Rats

Hoffmann

Böker

Schneider

et al. 2016

Molecular Therapy - Nucleic Acids

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“…Using JC VLPs as delivery vectors has several advantages (30). The VLPs can be generated using E. coli, and are available in large quantities and at low cost.…”

Section: Discussionmentioning

confidence: 99%

Targeting the IL-10 Pathway by RNA Interference Has Beneficial Effects on the Development of Experimental Lupus

et al. 2013

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The first two authors contributed equally to this workResults from patients with systemic lupus erythematosus (SLE) and from mice suffering from a lupus-like disease suggest that the IL-I0 pathway is involved in pathogenesis, and that this cytokine could represent a target for managing SLE development. In this study, we constructed JC virus-like particles (VLP) expressing IL-I0-specific short hairpin RNAs (shRNAs) that efficiently silenced IL-I0 gene expression. In mice, a single injection of this preparation dramatically reduced serum levels of IL-10. We tested the preventive effect of this vector expressing anti-IL-I0 shRNAs in female (NZBxNZW) F 1 mice. Weekly intraperitoneal injections decreased the incidence and severity of proteinuria, and prolonged lifespan, with reduced IL-I0 production. Our data demonstrate that the IL-I0 pathway plays a chief role in lupus pathogenesis. It indicates that JC virus-like particles represent a potent vector for delivering interfering RNA in vivo. They suggest that RNA interference targeting IL-I0 is an effective strategy to silence the IL-I0 pathway, and possesses a therapeutic potential that could be useful in the management of SLE and, possibly, other immune-mediated disorders.

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“…It can be easily generated in large quantities and at low cost. Exogenous genes can be packaged by the VLP and then delivered to cells susceptible to JC polyomavirus (JCPyV) for gene transduction [3]. …”

Section: Introductionmentioning

confidence: 99%

Recombinant VLP-Z of JC Polyomavirus: A Novel Vector for Targeting Gene Delivery

Deng

Zeng²,

Su³

et al. 2015

Intervirology

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Virus-like particle (VLP) of JC polyomavirus (JCPyV) is capable of packaging and delivering exogenous DNA into human cells and can be used for mediating therapeutic gene expression. However, many human cells express the JCPyV receptor. Thus, wild-type VLP can transduce a wide range of human cells nonspecifically. This study tested the feasibility of using a modified VLP with a IgG binding domain (Z domain) of protein A in its capsid for targeted gene delivery. The Z domain of protein A isolated from the membrane of Staphylococcus aureus was inserted into the NH₃-terminus of VP_1, the major JCPyV capsular protein. The recombinant VLP-Z was produced using Escherichia coli. Electron-microscopic analysis showed that VLP-Z has a viral-like structure. A hemagglutination test showed that VLP-Z has hemagglutination activity. VP₁ was detected in the nuclei of HeLa cells by immunostaining after VLP-Z inoculation, suggesting that VLP-Z is viable and can enter the cell nucleus. Inoculating HeLa cells with pEGFP-N₁ plasmid packaged in VLP-Z has resulted in enhanced green fluorescent protein expression in the cells. In addition, a binding assay showed that VLP-Z was able to bind IgG through the interaction of the Z domain in VLP-Z and IgG. These data suggest that VLP-Z could be armed with cell-specific antibody and be used to deliver therapeutic genes to target cells.

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Human JC virus-like particles as a gene delivery vector

Cited by 26 publications

References 68 publications

In Vivo siRNA Delivery Using JC Virus-like Particles Decreases the Expression of RANKL in Rats

In Vivo siRNA Delivery Using JC Virus-like Particles Decreases the Expression of RANKL in Rats

Targeting the IL-10 Pathway by RNA Interference Has Beneficial Effects on the Development of Experimental Lupus

Recombinant VLP-Z of JC Polyomavirus: A Novel Vector for Targeting Gene Delivery

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