Anticipating and Identifying Collateral Damage in Genome Editing

• Published in: Trends in genetics 2020-12, Vol.36 (12), p.905-914
• Main Authors: Burgio, Gaëtan, Teboul, Lydia
• Format: Article
• Language: English
• Subjects: Animals; CRISPR-Cas Systems; ectopic insertions; Gene Editing - standards; Genome; genome editing; Humans; off-target activity; on-target activity; Risk Assessment; validation
• ISSN: 0168-9525
• DOI: 10.1016/j.tig.2020.09.011

Genome editing has powerful applications in research, healthcare, and agriculture. However, the range of possible molecular events resulting from genome editing has been underestimated and the technology remains unpredictable on, and away from, the target locus. This has considerable impact in providing a safe approach for therapeutic genome editing, agriculture, and other applications. This opinion article discusses how to anticipate and detect those editing events by a combination of assays to capture all possible genomic changes. It also discusses strategies for preventing unwanted effects, critical to appraise the benefit or risk associated with the use of the technology. Anticipating and verifying the result of genome editing are essential for the success for all applications. Genome editing has a transformative potential in healthcare or to improve crops or livestock. However, the use of Cas9 or other nucleases can yield unpredictable events at the target site or off target.To overcome these challenge, it is critical to understand and accurately predict the whole range of possible editing outcomes.The key to success is to combine molecular assays to evaluate the sequence changes at the target site and to quantify the number of copies of segments deleted/inserted across the genome.For all applications, thorough evaluation of these outcomes is essential to identify all collateral damage from nuclease activity and for a real appraisal of the benefits and risks associated with applying this technology.