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Investigation of an Oncolytic MeV Cell-Cell Fusion Phenomenon Induced by an siRNA

Oncolytic measles virus is a promising cancer therapeutic in clinical trials which
possesses multiple characteristics that are advantageous over traditional therapies.
Currently, clinical oncolytic measles virus vectors are unmodified or express reporter
transgenes that benefit its therapeutic efficacy. The next phase in its development will
see genetically engineered vectors encoding transgenes that enhance its antineoplastic effects. To this end, preclinical research has focused on studying novel transgenes which favour viral replication, cytotoxicity, and the anti-cancer immune response. We sought to encode artificial micoRNAs targeting RIG-I as a strategy to interfere with innate immunity. Silencing RIG-I with multiple siRNAs yielded one which promotes measles virus syncytia formation through a mechanism that appears to be independent of RIG-I. The mechanism caused by the siRNA leads to enhanced measles virus cell-cell fusion and has peculiar characteristics which are not fully understood.

Identiferoai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/41531
Date02 December 2020
CreatorsBarkley, Russell
ContributorsBell, John, Alain, Tommy
PublisherUniversité d'Ottawa / University of Ottawa
Source SetsUniversité d’Ottawa
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Formatapplication/pdf

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