Mutational rescue of the activity of high-fidelity Cas9 enzymes

Programmable DNA endonucleases derived from bacterial genetic defense systems, exemplified by CRISPR-Cas9, have made it significantly easier to perform genomic modifications in living cells. However, unprogrammed, off-target modifications can have serious consequences, as they often disrupt the function or regulation of non-targeted genes and compromise the safety of therapeutic gene editing applications.

Citation:
Vos PD, Gandadireja AP, Rossetti G, Siira SJ, Mantegna JL, Filipovska A, Rackham O. Mutational rescue of the activity of high-fidelity Cas9 enzymes. Cell Rep Method. 2024;4(4).

Keywords:
CP: Biotechnology; CP: Molecular biology; CRISPR; Cas9; HypaCas9; TurboCas9; gene editing; gene therapy; genome modification; off target; protein engineering; synthetic biology

Abstract:
Programmable DNA endonucleases derived from bacterial genetic defense systems, exemplified by CRISPR-Cas9, have made it significantly easier to perform genomic modifications in living cells. However, unprogrammed, off-target modifications can have serious consequences, as they often disrupt the function or regulation of non-targeted genes and compromise the safety of therapeutic gene editing applications.