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Coxsackievirus B3 (CVB3) has potential as a new oncolytic agent for the treatment of cancer but can induce severe pancreatitis. Here, we inserted target sequences of the microRNA miR-375 (miR-375TS) into the 5′ terminus of the polyprotein encoding sequence or into the 3′UTR of the CVB3 strain rCVB3.1 to prevent viral replication in the pancreas. In pancreatic EndoC-βH1 cells expressing miR-375 endogenously, replication of the 5′-miR-375TS virus and that of the 3′-miR-375TS virus was reduced by 4 × 103-fold and 3.9 × 104-fold, respectively, compared to the parental rCVB3.1. In colorectal carcinoma cells, replication and cytotoxicity of both viruses were slightly reduced compared to rCVB3.1, but less pronounced for the 3′-miR-375TS virus. Thus, CVB3 with miR-375TS in the 3′UTR of the viral genome may be suitable to avoid pancreatic toxicity.

Original publication

DOI

10.1002/1873-3468.13647

Type

Journal article

Journal

FEBS Letters

Publication Date

01/02/2020

Volume

594

Pages

763 - 775