2026-10-12T01:54:20Z https://www.scidb.cn/oai

10.57760/sciencedb.35870 2026-01-21T15:30:27Z

2026-01-21 Coiled-coil heterodimer-mediated split base editing systems enable flexible and robust nucleotide substitutions doi:10.57760/sciencedb.35870 en Base editors (BEs) enable precise base substitutions, but their size exceeds the packaging capacity of adeno-associated virus (AAV), impeding in vivo applications. Here we design a split BE system that recruits deaminases to Cas9 nickase via coiled-coil heterodimers, resulting in various coiled-coil heterodimers-mediated base editors (CC-BEs), including cytidine base editor (CC-CBE), adenine base editor (CC-ABE), and their derivatives. We reveal that CC-BEs maintain and even improve the editing efficiency of the original unsplit BEs across various cell types and editing scopes, achieving maximum enhancements of 9.6-fold in human immortalized cells and 12.4-fold in primary somatic cells for CC-CBE. Using CC-ABE, we validate in vivo editing efficiency and successfully achieve A-to-G conversion in the Pcsk9 and Dmd genes via dual-AAV vectors in mice. Altogether, we develop a simple and universal strategy to address the challenges posed by the large size of BEs without compromising editing efficiency for base substitutions in vivo. Coiled-coil; base editing; split; flexible Qin Jin Liangxue Lai Kepin Wang Hui Shi PUBLIC https://creativecommons.org/publicdomain/zero/1.0/ dataset http://www.doi.org/10.1038/s41467-026-68469-2 Science Data Bank