Translating base editors: a decade of progress from the bench to the clinic

A decade has passed since the initial description of cytosine base editors in 2016. This new class of gene editors, utilizing DNA damage intermediates beyond double-stranded DNA breaks, fundamentally shifted the paradigm of gene editing from stochastic disruption to precise chemical correction. Since then, the field has rapidly matured, with the development of optimized base editors with improved editing efficiency, targeting scope, precision and specificity, as well as the subsequent generation of adenine base editors and prime editors. Base editors have not only become widely used research tools but have served as foundational platforms for biotechnology companies developing human therapies. Today, base editors are being deployed in trials for a diverse list of indications including sickle cell disease, alpha-1 antitrypsin deficiency, inborn errors of metabolism, leukaemias and cardiovascular indications. This Review critically examines the 'bench-to-bedside' trajectory of base editors, detailing their mechanistic evolution and expanding role in treating human disease.