Enhanced genomic stability of new miRNA-regulated oncolytic coxsackievirus B3.

ABSTRACT: Genetic modification of coxsackievirus B3 (CVB3) by inserting target sequences (TS) of tumor-suppressive and/or organ-selective microRNAs (miRs) into viral genome can efficiently eliminate viral pathogenesis without significant impacts on its oncolytic activity. Nonetheless, reversion mutants (loss of miR-TS inserts) were identified as early as day 35 post-injection in ∼40% immunodeficient mice. To improve the stability, here we re-engineered CVB3 by (1) replacing the same length of viral genome at the non-coding region with TS of cardiac-selective miR-1/miR-133 and pancreas-enriched miR-216/miR-375 or (2) inserting the above miR-TS into the coding region (i.e., P1 region) of viral genome. Serial passaging of these newly established miR-CVB3s in cultured cells for 20 rounds demonstrated si

SUBMITTER: Liu H 

PROVIDER: S-EPMC9593271 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature