Optimized dual-AAV base editor delivery system with enhanced editing efficiency and virion production titer.

ABSTRACT: Base editors (BEs) are a promising tool for precise base conversion in human cells and animals, while the adeno-associated virus (AAV) is the major vector for human gene therapy. However, the size of the DNA cassette required for BE expression exceeds the 4.7 kb packing capacity of the AAV vector, making dual-AAV approaches based on trans-splicing intein necessary. Even with this approach, current split DNA cassettes are still larger than the AAV packing limit, posing a challenge for cellular production of AAV. Moreover, some split strategies yield variable editing results and target coverage. To address these limitations, 25 different split sets for BE4max and A3A-BE4max were tested at two target sites respectively, with splitting sites ranging from 493rd to 517th amino acids on th

SUBMITTER: Yu W 

PROVIDER: S-EPMC12002711 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature