Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety

被引：31

作者：

Teboul, Lydia ^{[1
]}

Herault, Yann ^{[2
]}

Wells, Sara ^{[1
]}

Qasim, Waseem ^{[3
]}

Pavlovic, Guillaume ^{[2
]}

机构：

[1] MRC, Mary Lyon Ctr, Harwell Inst, Harwell Campus, Didcot OX11 0RD, Oxon, England

[2] Univ Strasbourg, CNRS, INSERM, IGBMC,PHENOMIN Inst Clin Souris, F-67404 Strasbourg, France

[3] NIHR Biomed Res Ctr, Great Ormond St Inst Child Hlth, London WC1N 1EH, England

来源：

MOLECULAR THERAPY | 2020年 / 28卷 / 06期

基金：

英国医学研究理事会;

关键词：

OFF-TARGET CLEAVAGE; STRAND BREAK REPAIR; GENE-THERAPY; CRISPR/CAS9; CRISPR-CAS9; MUTATIONS; VECTOR; MOUSE; MICE; GENERATION;

D O I：

10.1016/j.ymthe.2020.03.015

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：

Genome editing tools have already revolutionized biomedical research and are also expected to have an important impact in the clinic. However, their extensive use in research has revealed much unpredictability, both off and on target, in the outcome of their application. We discuss the challenges associated with this unpredictability, both for research and in the clinic. For the former, an extensive validation of the model is essential. For the latter, potential unpredicted activity does not preclude the use of these tools but requires that molecular evidence to underpin the relevant risk:benefit evaluation is available. Safe and successful clinical application will also depend on the mode of delivery and the cellular context.

引用

页码：1422 / 1431

页数：10

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