It is important to develop consensus guidelines for defining off-target mutations in DNA, which could occur as an unintended side-effect of genome editing (see Nature 522, 20–24; 2015). I encourage the community to contribute to these discussions (see go.nature.com/zncbil).
Such uniform standards would help researchers, peer-reviewers, journal editors and regulators to best identify such mutations.
For therapeutic applications, unwanted mutations need to be defined by the most highly sensitive, unbiased genome-wide methods — given that even low-frequency events in large populations of cells could have clinical consequences. Such a comprehensive definition might not be necessary for research projects because appropriate control experiments would exclude the potentially confounding effects of off-target actions.
For now, direct comparison of state-of-the-art technologies can start to define best practices. Refinement will follow as detection and editing methodologies advance.
J.K.J is a consultant for Horizon Discovery, has financial interests in Editas Medicine, Hera Testing Laboratories, Poseida Therapeutics and Transposagen Biopharmaceuticals. These interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies.
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