Bacterial toxins represent a vast reservoir of biochemical diversity that can be repurposed for biomedical applications. Here, we report the discovery of a novel bacterial toxin that catalyzes the unprecedented deamination of cytidines within double-stranded DNA. All previously described cytidine deaminases operate on single-stranded DNA and thus when applied to genome editing require unwinding of dsDNA by macromolecules such as CRISPR-Cas9 complexed with a guide RNA. Engineering this novel bacterial toxin resulted in RNA-free programmable cytosine base editors that catalyze CG-to-TA conversions efficiently and with high DNA sequence specificity and product purity at a variety of targeted sites in human cells. CRISPR-free base editing enables precise manipulation of DNA when RNA delivery is not possible.

Novel bacterial toxin enables CRISPR-free, RNA-free base editing

ACS Fall 2020 Virtual Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.