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Vesicular Stomatitis Virus (VSV) Service


Creative Biogene has launched vesicular stomatitis virus (VSV) services in order to accelerate VSV-based studies...

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Vesicular Stomatitis Virus (VSV) Service

Creative Biogene has launched vesicular stomatitis virus (VSV) services in order to accelerate VSV-based studies in the area of cancer therapy, neuronal tracing and so on.

VSV Introduction

Vesicular stomatitis virus (VSV) is a prototypic non-segmented, negative-strand RNA virus in the genus of Vesiculovirus of the family Rhabdoviridae. The VSV genome is comprised of approximately 11,000 nucleotides which encodes five major viral proteins including G protein (G), large protein (L), phosphoprotein (P), matrix protein (M) and nucleoprotein (N).

Figure 1. Vesicular stomatitis virus (VSV)

VSV can infect a wide range of host cells and its lifecycle occurs in the cytoplasm of host cells. However, replication of VSV is limited to cells that are impaired in their interferon (IFN) pathways, and IFN in most cancer cells are believed to be impaired. This feature allows VSV to preferentially replicate in cancer cells and further destroy them. Results from preclinical studies have also demonstrated that VSV is a promising candidate in oncolytic virus (OV) therapy. Another wide use of VSV is tracing neuronal connections in vivo to elucidate the mechanisms of nervous system in information processing.

VSV Design & Production

There are several advantages that make VSV a powerful tool in scientific research and clinical therapy, including well-characterized biology, small and easily manipulated genome, inherent tumor specificity, rapid replication, not pathogenic to humans etc. Creative Biogene has established an efficient VSV platform for creating recombinant VSVs based on our experienced staffs and our advanced molecular biology techniques especially reverse genetics tools. So far, our VSV platform has successfully engineered various recombinant VSVs for use in anticancer and neural tracing studies. Scientists at Creative Biogene are happy to satisfy your needs in VSV design and production.

Figure 2. Green fluorescent image of cells infected with VSV-GFP.

Approaches

MicroRNA Targeting

The host often produces microRNAs (miRNAs) that exacerbate viral pathogenesis in a tissue-specific manner. The best approach to counteract a specific miRNA is the generation of a complementary RNA (cRNA) sequence against said miRNA, where a viral gene delivery approach is used. In this approach, an attenuated rVSV was created by incorporating miR-125-specific cRNA sequences in the 3’ UTR region of the viral genome which showed significantly lower neuropathogenesis.

Modifications of M

VSV reverse genetics systems are well established and many advances have been done to precisely edit the viral genome. To ameliorate neuropathogenicity, appropriate genome modifications efforts were made to create recombinant viruses (rVSVs) with desirable oncolytic activities. Initially, the matrix protein was mutated. The ΔM51 mutant created by deletion of methionine at 51st position (VSVΔM51) showed reduced cytotoxicity and was found to be ineffective in blocking IFNs (IFN-α) expression in the infected cells.

Modification of G

To counter neurotoxic and immunostimulatory effects associated with the G protein, a mutational approach for G modification has been explored. Various point mutations in G were created (G5, G6, and G6R). These virions showed effective oncolysis of gliomas with minimal toxic effects to neurons as compared to wt-VSV, and were therefore experimentally used as an adjuvant to surgical treatment of high-grade gliomas.

Modulating Viral Replication

Combinations of the VSVΔG vector with either of the two trans-complementing deletion mutants of VSV polymerase L (VSVΔL) or phosphoprotein P (VSVΔP) or the mutual combination of VSVΔP/VSVΔL vectors were co-administrated to reduce neurotoxicity and attenuate viral pathogenesis. The resultant vector replication was proven to be safe in the host, with only a marginal reduction in its antitumor efficacy.

0403_VSV.jpgFigure 3. Reverse genetics use in making customized VSV targeting tumor lysis.(Viruses 2018)

Creative Biogene has the ability to modify your VSV product based on your need. With our platform, we could provide one-stop service for your virus-related project.

Applications

  • Gene delivery
  • Neural tracing studies
  • Study and design oncolytic viruses

Our Service Includes

Figure 4. Service workflow

References

  1. Hastie E, Grdzelishvili VZ. Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer. J Gen Virol. 2012 Dec;93(Pt 12):2529-45.
  2. Beier KT, Saunders A, Oldenburg IA, Miyamichi K, Akhtar N, Luo L, Whelan SP, Sabatini B, Cepko CL. Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15414-9.
  3. Bishnoi, S., Tiwari, R., Gupta, S., Byrareddy, S.N., Nayak, D. Oncotargeting by Vesicular Stomatitis Virus (VSV): Advances in cancer therapy. Viruses. 2018; 10(2): 90.

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