MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.

ABSTRACT: MicroRNAs are small non-coding RNA molecules that regulate mRNA translation and stability by binding to complementary sequences usually within the 3' un-translated region (UTR). We have previously shown that the hepatic toxicity caused by wild-type Adenovirus 5 (Ad5WT) in mice can be prevented by incorporating 4 binding sites for the liver-specific microRNA, mir122, into the 3' UTR of E1A mRNA. This virus, termed Ad5mir122, is a promising virotherapy candidate and causes no obvious liver pathology. Herein we show that Ad5mir122 maintains wild-type lytic activity in cancer cells not expressing mir122 and assess any effects of possible mir122 depletion in host cells. Repeat administration of 2×10(10) viral particles of Admir122 to HepG2 tumour bearing mice showed significant anti-cancer effi

SUBMITTER: Cawood R 

PROVIDER: S-EPMC3018484 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature