Life Sciences & Biotechnology
Title : | Molecular characterization of the cytopathic property of Chandipura virus to engineer an attenuated oncolytic vector. |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. John Bernet Johnson, Rajiv Gandhi Centre For Biotechnology (RGCB), Kerala |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | johnbjohnson@rgcb.res.in |
Equipments : | pH meter
Luminometer |
Details
Executive Summary : | Cancer is a growing global burden, with increasing mortality and morbidity rates. Despite the existence of innovative treatments, the complexity of tumor microenvironments necessitates customized treatment. This proposal focuses on oncolytic virotherapy, an area with great interest globally. India is currently behind in this area. The study proposes to exploit the cytopathic properties of Chandipura virus (CHPV) to develop it into a potent oncolytic vector. CHPV, a rhabdovirus, is a well-known human pathogen from the Indian subcontinent. The hypothesis is that CHPV based oncolytic vectors will be potent against brain cancers like glioblastoma. The study demonstrates that human cancer cell lines are differentially susceptible to wild type CHPV, demonstrating its ability to grow and induce more cell death in highly susceptible cell lines both in vitro and in vivo. CHPV satisfies key requirements of an oncolytic vector, including effectiveness at a low dose, restriction in normal cells, and induction of tumor regression. To exploit its oncolytic potential, CHPV should be significantly attenuated. The study aims to identify hotspots in the matrix and glycoprotein and engineer point mutations to assess their contribution to viral pathogenicity. An in-house reverse genetics approach will be generated to incorporate these mutations and develop an attenuated CHPV. Extensive characterization of the mutant in comparison to wild type CHPV will be carried out in human cancer cell lines, and oncolytic potential will be validated in a NOD-sCID mouse model. The CHPV model system adopted is under exploration, showing a positive index in preliminary investigations. The CHPV based oncolytic vector will be significant in understanding how viruses target cancer and developing a viable treatment option for hard-to-treat cancers. |
Total Budget (INR): | 54,31,924 |
Organizations involved