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MiR-375-mediated suppression of engineered coxsackievirus B3 in pancreatic cells.
FEBS Lett. 594, 763-775 (2019)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cancer Therapy ; Colorectal Cancer ; Coxsackievirus B3 ; Microrna ; Oncolytic Virus; Enteroviral Rna; Virus; Micrornas; Strain; Picornavirus; Encephalitis; Virulence; Tissue
ISSN (print) / ISBN
0014-5793
e-ISSN
1873-3468
Journal
FEBS Letters
Quellenangaben
Volume: 594,
Issue: 4,
Pages: 763-775
Publisher
Elsevier
Publishing Place
111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute for Pancreatic Beta Cell Research (IPI)