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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animal Experimentation
  • Animals
  • CRISPR-Cas Systems
  • Clinical Studies as Topic
  • Gene Editing / methods*
  • Gene Editing / standards*
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods
  • Genetic Therapy / standards
  • Humans
  • Organ Specificity
  • Reproducibility of Results
  • Risk Assessment
  • Translational Research, Biomedical / methods
  • Translational Research, Biomedical / standards