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.
Genome editing tools have already revolutionized biomedical research and will have a major impact in the clinic. However, the unpredictability of genome editing outcomes raises the question of its safety for human therapy. This article reviews molecular evidences both in animals models and human and their implications for risk:benefit evaluation.