Adenine base editor-based correction of the cardiac pathogenic Lmna c.1621C > T mutation in murine hearts
Key Finding
Developed all-in-one S. aureus Cas9-based ABE8e (SaABE8e) that fits in single AAV vector for cardiac gene therapy. Demonstrated that compact SaCas9 (~1 kb smaller than SpCas9) enables single-AAV delivery of complete adenine base editor, eliminating dual-AAV co-transduction requirements. Validated ABE editing efficiency with different TadA variants (7.10 vs 8e) and PAM variants (NG vs SpG) for correcting pathogenic Lmna mutations in mouse hearts.