Study on Genetically Engineered Vesicular Stomatitis Virus for the Application of Treating Malignant Diseases using Gene Therapy

Abstract

Vesicular Stomatitis Virus (VSV) is a non-pathogenic negative stranded RNA enveloped virus which is genetically engineered to generate recombinant VSV producing suicide gene product, thymidine kinase (TK) or cytokine interleukin 4(IL-4). To target cancer cells or to stimulate immunity against diseases such as AIDS or influenza, the VSV is engineered which is ascetically harmless. The recombinant virus induces apoptosis in the cancerous cells while the normal cells are protected by the interferons and has the effective oncolytic activity, both in vitro and in vivo. When injected in vitro, high level of biologically active TK and IL-4 is and no defects in replication are observed. VSV leukemolytic properties is well established in treating leukemia cell lines by killing it efficiently, keeping the normal clonogenic bone marrow progenitor cells remarkably safe from VSV infection. Recombinant VSV is employed as an emerging anti-cancer approach. To improve oncoselectivity, safety, oncotoxicity and stimulus of tumor-specific immunity, VSV-based recombinant viruses have been engineered through reverse genetics. A complete decrease in the number of tumors as well as the high anti-tumor activity in the malignant disease was observed. The recombinant VSV is a methodology to various other malignant diseases, those anchorages a range of genetic defects and neoplastic diseases.