Adenine base editing delivered via AAV9 achieved partial correction of the LMNA mutation in HGPS mice, rescuing structural bone defects and normalizing gene expression when administered at two weeks of age. This demonstrates that in vivo base editing can address monogenic bone disorders and establishes timing-dependent efficacy for genetic correction strategies.
Key Points
- AAV9-delivered base editor corrected ~22% of mutations in bone at optimal timing
- Treatment rescued bone structure and mineralization capacity in HGPS mice
- Early intervention (P14) yielded superior outcomes; later treatment showed minimal correction
Longevity Analysis
Progeria accelerates deterioration across multiple tissues including bone, cardiovascular system, and skin through accumulation of dysfunctional protein. This work establishes that direct mutation correction at the DNA level can partially restore normal tissue function and gene regulation—a principle with implications for other single-gene aging phenotypes. The critical finding is timing: the window for effective intervention appears narrow, suggesting that early detection and rapid therapeutic deployment will be essential for genetic correction strategies targeting age-related structural decline.
Original published by Wiley Aging Cell, by Wayne A. Cabral, Caleb M. Grenko, Diana Yeritsyan, Indeevar Beeram, Shubham Laiwala, Lukas R. Johnson, Urraca L. Tavarez, Tingfen Yan, Stephen M. Wincovitch, Luke W. Koblan, Xin D. Gao, Meirui An, Narisu Narisu, Leslie G. Biesecker, David R. Liu, Ara Nazarian, Francis S. Collins, Michael R. Erdos .