Anticipating and Identifying Collateral Damage in Genome Editing

Abstract

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.

Keywords: ectopic insertions; genome editing; off-target activity; on-target activity; validation.

Figure1:. Possible outcomes of Cas9 double stranded break of the DNA:

Cas9 induced double stranded break leads to a series of expected and unexpected outcomes. Final editing outcome results in small insertions, deletions or chromosomal translocations or incomplete template integration.