A let-7 microRNA-sensitive vesicular stomatitis virus demonstrates tumor-specific replication

被引：106

作者：

Edge, Robert E. ^{[1
]}

Falls, Theresa J. ^{[1
]}

Brown, Christopher W. ^{[1
]}

Lichty, Brian D. ^{[2
]}

Atkins, Harold ^{[1
]}

Bell, John C. ^{[1
]}

机构：

[1] Univ Ottawa, Ottawa Hlth Res Inst, Dept Biochem Microbiol & Immunol, Ctr Canc Therapeut, Ottawa, ON K1H 8L6, Canada

[2] McMaster Univ, Michael DeGroote Ctr Learning & Discovery, Ctr Gene Therapeut, Dept Pathol & Mol Med, Ottawa, ON, Canada

来源：

MOLECULAR THERAPY | 2008年 / 16卷 / 08期

关键词：

D O I：

10.1038/mt.2008.130

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Creation of potent oncolytic viruses (OVs) suitable for the clinic may require new strategies in virus design. Replication-competent viruses facilitate a variety of approaches to achieving tumor specificity. Altered expression of microRNAs is a common hallmark of cancer that we demonstrate can be used to alter expression of a potent wild-type viral gene to achieve tumor-specific replication of an engineered vesicular stomatitis virus (VSV). Incorporation of let-7 microRNA complementary sequences within VSV eliminates undesirable replication and associated toxicity in normal cells but permits growth in cancer cells in vitro and in vivo. This is proof of concept that viruses designed to exploit the differential microRNA expression in cancer cells is a viable approach, potentially useful in optimizing oncolytic viral gene expression for maximal antitumor activity and safety.

引用

页码：1437 / 1443

页数：7

共 49 条

[1] Sensitivity of prostate tumors to wild type and M protein mutant vesicular stomatitis viruses [J].