Format

Send to

Choose Destination
FEBS Lett. 2019 Oct 23. doi: 10.1002/1873-3468.13647. [Epub ahead of print]

MiR-375-mediated suppression of engineered coxsackievirus B3 in pancreatic cells.

Author information

1
Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Germany.
2
Paul Langerhans Institute Dresden, Helmholtz Center Munich, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
3
Corporate Member of Freie Universität Berlin, Berlin Institute of Health (BIH), Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Germany.

Abstract

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.

KEYWORDS:

cancer therapy; colorectal cancer; coxsackievirus B3; microRNA; oncolytic virus

PMID:
31643074
DOI:
10.1002/1873-3468.13647

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center