Adenine base editor-based correction of the cardiac pathogenic Lmna c.1621C > T mutation in murine hearts.

ABSTRACT: Base editors are emerging as powerful tools to correct single-nucleotide variants and treat genetic diseases. In particular, the adenine base editors (ABEs) exhibit robust and accurate adenine-to-guanidine editing capacity and have entered the clinical stage for cardiovascular therapy. Despite the tremendous progress using ABEs to treat heart diseases, a standard technical route toward successful ABE-based therapy remains to be fully established. In this study, we harnessed adeno-associated virus (AAV) and a mouse model carrying the cardiomyopathy-causing Lmna c.1621C > T mutation to demonstrate key steps and concerns in designing a cardiac ABE experiment in vivo. We found DeepABE as a reliable deep-learning-based model to predict ABE editing outcomes in the heart. Screening of sgRNAs for

SUBMITTER: Yang L 

PROVIDER: S-EPMC10853587 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature