Base editing for precision therapeutics.

Moksada Regmi; Kuiying Ma; Changhao Bi; Xueli Zhang; Dongdong Zhao; Lingling Yu; Huihui Yang; Ningli Wang; Chenlong Yang

doi:10.1016/j.xgen.2026.101298

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Base editing for precision therapeutics.

Moksada Regmi·Kuiying Ma·Changhao Bi·Xueli Zhang·Dongdong Zhao·Lingling Yu·Huihui Yang·Ningli Wang·Chenlong Yang

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Abstract

Base editing (BE), the precise installation of single-nucleotide changes in DNA or RNA without inducing double-strand breaks, holds substantial therapeutic promise for correcting single-nucleotide variants, which constitute more than half of the known pathogenic genetic variants. Recent advances have improved base editor specificity, efficiency, and delivery, enabling clinically oriented procedures. Clinically, BE has shown early success or strong translational promise in sickle cell disease, β-thalassemia, leukemia (via CAR T and epitope engineering), hypercholesterolemia (PCSK9 and ANGPTL3), alpha-1-antitrypsin deficiency, and glycogen storage disease type Ia. Key remaining challenges include bystander editing within the activity window, residual off-target DNA and RNA editing, delivery constraints (payload size, tissue targeting, and redosing limits), immunogenicity, and the need for durable long-term safety evidence across relevant cell types and disease contexts. Continued technological refinements, careful preclinical validation, and rigorous clinical assessment will be essential to fully realize BE's transformative potential in precision medicine.

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Humans Precision Medicine Gene Editing Animals Genetic Therapy CRISPR-Cas Systems CRISPR-Cas systems base editing gene therapy delivery genome engineering precision therapeutics single-nucleotide correction Journal Article Review

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Moksada Regmi, Kuiying Ma, Changhao Bi, Xueli Zhang, Dongdong Zhao, Lingling Yu, Huihui Yang, Ningli Wang, Chenlong Yang. 2026-07-22. Base editing for precision therapeutics.. https://doi.org/10.1016/j.xgen.2026.101298

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