Basemodifying

Basemodifying is a term used to describe techniques that change the chemical bases of nucleic acids, primarily DNA or RNA, to produce precise nucleotide substitutions without relying on double-strand breaks. It encompasses DNA base editing and RNA base editing and is a subset of programmable nucleic acid modification. The goal is to alter genetic information with high specificity while minimizing unintended genome disruption.

In DNA basemodifying, enzymes such as deaminases are fused to programmable DNA-targeting systems like dead or nicking variants of CRISPR-associated nucleases. Cytosine base editors convert a C•G base pair to a T•A pair, while adenine base editors change an A•T pair to a G•C pair. These edits occur within a defined editing window and are typically followed by cellular repair processes that finalize the substitution. Advances have produced variants with improved fidelity, broader target compatibility, and reduced off-target activity. DNA basemodifying aims to create precise point mutations without introducing double-strand breaks, which can reduce large rearrangements and unwanted deletions.

RNA basemodifying applies similar concepts to RNA, often using programmable guides to recruit editing enzymes that convert one RNA base to another. Since RNA edits are not permanent in the genome, they offer reversible, transient modifications with distinct therapeutic and research implications.

Applications of basemodifying include functional genomics studies, disease modeling, crop improvement, and potential therapeutic interventions. Limitations include off-target edits, context dependence of editing efficiency, dependence on targetable PAM sequences, and concerns about long-term safety and ethics. Ongoing research seeks to expand targeting scope, improve accuracy, and address regulatory considerations as these technologies move toward clinical and agricultural use.