Targeted nonviral delivery of genome editors in vivo.

Cell-type-specific in vivo delivery of genome editing molecules is the next breakthrough that will drive biological discovery and transform the field of cell and gene therapy. Here, we discuss recent advances in the delivery of CRISPR-Cas genome editors either as preassembled ribonucleoproteins or encoded in mRNA. Both strategies avoid pitfalls of viral vector-mediated delivery and offer advantages including transient editor lifetime and potentially streamlined manufacturing capability that are already proving valuable for clinical use. We review current applications and future opportunities of these emerging delivery approaches that could make genome editing more efficacious and accessible in the future.
Competing Interests: Competing interests statement:J.A.D. is a co-founder of Editas Medicine, Intellia Therapeutics, Caribou Biosciences, Mammoth Biosciences, and Scribe Therapeutics. J.R.H. and J.A.D. are co-founders of Azalea Therapeutics. J.A.D is a scientific advisory board member of Intellia Therapeutics, Caribou Biosciences, Mammoth Biosciences, Scribe Therapeutics, Vertex Pharmaceuticals, eFFECTOR Therapeutics, Felix Biosciences, The Column Group, Inari, and Isomorphic Labs. J.A.D. is the Chief Science Advisor at Sixth Street, an advisor at Tempus, and a Director at Johnson & Johnson and Altos Labs. The Regents of the University of California have patents issued and/or pending related to CRISPR technologies and delivery technologies on which C.A.T., J.R.H., and J.A.D. are listed inventors. J.A.D. has sponsored research projects through Biogen, Pfizer, Apple Tree Partners, Genentech, and Roche.