baseediting

Base editing is a genome editing approach that enables precise conversion of a single DNA base into another without introducing double-strand breaks. It uses engineered enzymes that couple a DNA-targeting protein to a deaminase enzyme to perform a chemical change on a base, producing a predictable base substitution after DNA replication.

Two main families exist: cytidine base editors (CBEs) convert cytosine to thymine (C to T on the opposite strand), and adenine base editors (ABEs) convert adenine to guanine (A to G). CBEs typically use a cytidine deaminase fused to a Cas9 nickase, along with an inhibitor of base-excision repair to preserve the edited base. ABEs use an evolved adenine deaminase fused to Cas9 nickase. The targeting is guided by a guide RNA that directs the complex to a protospacer adjacent motif, and editing occurs within a defined window of nucleotides in the target region.

Variants and improvements have followed, including BE3, BE4, and BE4max for CBEs, and ABEs with enhanced fidelity. These developments aim to increase editing efficiency, broaden PAM compatibility, and reduce unwanted edits. Some base editors also pair Cas9 variants with expanded PAMs or alternative deaminases to reach more sites.

Limitations include dependence on PAM presence, a limited editing window that can produce bystander edits, and potential off-target effects at DNA or, in some CBEs, RNA. Delivery method, expression levels, and cell type influence efficiency and safety, and there is ongoing assessment of long-term effects.

Applications include basic research on gene function, disease modeling, therapeutic development, and agricultural genetics. As with all genome editing approaches, ethical, regulatory, and safety considerations guide clinical and environmental use.