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Review
. 2020 Jun 3;28(6):1422-1431.
doi: 10.1016/j.ymthe.2020.03.015. Epub 2020 Mar 20.

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

Lydia Teboul  1 , Yann Herault  2 , Sara Wells  3 , Waseem Qasim  4 , Guillaume Pavlovic  5
Affiliations
Review

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

Lydia Teboul et al. Mol Ther. .

Abstract

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.

Keywords: CRISPR/Cas9; clinical safety; functional genomics; gene delivery; gene therapy; medical research; research reproducibility.

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Figures

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Graphical abstract
Figure 1
Figure 1
Balancing Benefits and Risks of Use of GETs in the Clinic Each clinical path (cell therapy, somatic therapy, or early embryo treatment) carries its own, as well as common, risk factors. The ratio of benefit to risk of new therapies needs to be individually evaluated for each disease in combination with each therapeutic design.
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