Base Editing in Progeria

This article reviews the application of adenine base editing (ABE) as a therapeutic strategy for Hutchinson–Gilford progeria syndrome (HGPS), a premature-aging disorder caused by the LMNA c.1824C>T mutation. Using a CRISPR-based ABE system delivered via adeno-associated virus serotype 9 (AAV9), researchers corrected the mutation in up to 91% of patient fibroblasts in vitro, improving nuclear architecture and reducing progerin expression. In vivo experiments in a transgenic mouse model showed that a single injection of AAV9-ABE at postnatal day 14 corrected 20–60% of LMNA alleles across multiple tissues, preserved vascular smooth muscle cells, prevented arterial fibrosis, and extended lifespan by over twofold compared to controls. Despite low rates of off-target DNA edits, concerns persist about mutagenic risks including liver tumor formation, warranting further safety studies before human trials.

This article reviews the application of adenine base editing (ABE) as a therapeutic strategy for Hutchinson–Gilford progeria syndrome (HGPS), a premature-aging disorder caused by the LMNA c.1824C>T mutation. Using a CRISPR-based ABE system delivered via adeno-associated virus serotype 9 (AAV9), researchers corrected the mutation in up to 91% of patient fibroblasts in vitro, improving nuclear architecture and reducing progerin expression. In vivo experiments in a transgenic mouse model showed that a single injection of AAV9-ABE at postnatal day 14 corrected 20–60% of LMNA alleles across multiple tissues, preserved vascular smooth muscle cells, prevented arterial fibrosis, and extended lifespan by over twofold compared to controls. Despite low rates of off-target DNA edits, concerns persist about mutagenic risks including liver tumor formation, warranting further safety studies before human trials.