Frequent Endonuclease Cleavage at Off-target Locations In Vivo

被引：44

作者：

Petek, Lisa M.

Russell, David W. ^{[2
,3
]}

Miller, Daniel G. ^{[1
]}

机构：

[1] Univ Washington, Dept Pediat, Div Med Genet, ISCRM, Seattle, WA 98109 USA

[2] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98109 USA

[3] Univ Washington, Dept Biochem, Seattle, WA 98109 USA

来源：

MOLECULAR THERAPY | 2010年 / 18卷 / 05期

关键词：

ZINC-FINGER NUCLEASES; DOUBLE-STRAND BREAKS; ADENOASSOCIATED VIRUS VECTORS; MAMMALIAN-CELLS; INTEGRATION; PURIFICATION; TOXICITY; GENOME; SITES; TITER;

D O I：

10.1038/mt.2010.35

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：

Target-site DNA breaks increase recombination frequencies, however, the specificity of the enzymes used to create them remains poorly defined. The location and frequency of off-target cleavage events are especially important when rare-cutting endonucleases are used in clinical settings. Here, we identify non-canonical cleavage sites of I-SceI that are frequently cut in the human genome by localizing adeno-associated virus (AAV) vector-chromosome junctions, demonstrating the importance of in vivo characterization of enzyme cleavage specificity.

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收藏

页码：983 / 986

页数：4

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