“When Genome Editing Goes Off-Target: Detecting Unintended Mutations Could Improve DNA-Editing Strategies”, Hannah R. Kempton, Lei S. Qi2019-04-19 (gene editing)⁠:

Editing DNA in eukaryotic cells with CRISPR-based systems has revolutionized the genome engineering field. Cas (CRISPR-associated) endonucleases are directed to a particular location in the genome by a short guide RNA, providing an easily programmable strategy to target any section of DNA.

As of now, two CRISPR-based approaches can introduce targeted, permanent edits. DNA cleavage with the Cas endonuclease facilitates small insertions or deletions of nucleotides that can disable the targeted gene¹. A second modified “base editor” system can generate precise single-base mutations in the targeted DNA².

For both approaches, it is imperative that DNA modifications are made in the intended region (“on-target”) and not elsewhere in the genome (“off-target”). On pages 286, 289, and 292 of this issue, Wienert et al 2019, Zuo et al 2019, and Jin et al 2019, respectively, describe methods that identify off-target activities, which will be invaluable in therapeutic contexts as well as for stringent evaluation of future iterations of gene-editing tools.