Format

Send to

Choose Destination
Sci Rep. 2014 Apr 23;4:4750. doi: 10.1038/srep04750.

In vivo therapeutic potential of Dicer-hunting siRNAs targeting infectious hepatitis C virus.

Author information

1
1] Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan [2] Division of Gastroenterology, Showa University Fujigaoka Hospital, Yokohama, Japan [3] Present address, Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan [4].
2
1] Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Hokkaido 060-0812, Japan [2].
3
1] Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan [2].
4
Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa 247-8530, Japan.
5
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
6
1] Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan [2] Division of Gastroenterology, Showa University Fujigaoka Hospital, Yokohama, Japan.
7
Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
8
Division of Gastroenterology, Showa University Fujigaoka Hospital, Yokohama, Japan.
9
Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Hokkaido 060-0812, Japan.

Abstract

The development of RNA interference (RNAi)-based therapy faces two major obstacles: selecting small interfering RNA (siRNA) sequences with strong activity, and identifying a carrier that allows efficient delivery to target organs. Additionally, conservative region at nucleotide level must be targeted for RNAi in applying to virus because hepatitis C virus (HCV) could escape from therapeutic pressure with genome mutations. In vitro preparation of Dicer-generated siRNAs targeting a conserved, highly ordered HCV 5' untranslated region are capable of inducing strong RNAi activity. By dissecting the 5'-end of an RNAi-mediated cleavage site in the HCV genome, we identified potent siRNA sequences, which we designate as Dicer-hunting siRNAs (dh-siRNAs). Furthermore, formulation of the dh-siRNAs in an optimized multifunctional envelope-type nano device inhibited ongoing infectious HCV replication in human hepatocytes in vivo. Our efforts using both identification of optimal siRNA sequences and delivery to human hepatocytes suggest therapeutic potential of siRNA for a virus.

PMID:
24756133
PMCID:
PMC3996463
DOI:
10.1038/srep04750
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center