Base editing was invented by David Liu's laboratory at Harvard University and the Broad Institute in 2016, addressing a key limitation of conventional CRISPR editing. Standard Cas9 creates double-strand breaks that the cell repairs through error-prone pathways, often producing insertions and deletions rather than precise single-nucleotide changes. Base editors avoid this by using a catalytically impaired Cas9 (nickase) fused to a deaminase enzyme that chemically converts one base to another within a small editing window, enabling C-to-T or A-to-G transitions without cutting both DNA strands.
Beam Therapeutics, co-founded by David Liu, Feng Zhang, and J. Keith Joung, is the leading company advancing base editing toward clinical application. Beam's pipeline includes programs for sickle cell disease, T-cell acute lymphoblastic leukemia, and alpha-1 antitrypsin deficiency. Verve Therapeutics has used base editing to inactivate the PCSK9 gene in non-human primates, achieving durable cholesterol reduction with a single treatment, and has advanced its lead program VERVE-101 into clinical trials for heterozygous familial hypercholesterolemia.
The two major classes of base editors, cytosine base editors (CBEs) and adenine base editors (ABEs), together can install four of the twelve possible point mutations. Recent developments have expanded the toolkit with C-to-G base editors and glycosylase base editors that access additional transition types. Challenges including bystander editing within the activity window, off-target RNA editing, and delivery to target tissues continue to drive engineering improvements. Despite these challenges, base editing represents one of the most clinically advanced precision genome editing modalities.