Fig. 1
Programmable base editing rescues Hutchinson–Gilford progeria syndrome. a A single base mutation at 1824 locus in LMNA gene results in mis-splicing and subsequently translates into a truncated lamin A protein, termed progerin, which causes Hutchinson–Gilford progeria syndrome (HGPS). b ABEmax-VRQR corrected human LMNA mutation in two primary fibroblast cells derived from HGPS patients. Using the lentiviral delivery delivered ABEmax-VRQR and sgRNA targeting LMNA c.1824 C > T mutation, resulting in gene editing of the LMNA loci and subsequently rescuing lamin A abundance and nuclear morphology. c ABEmax-VRQR treatment in HGPS mice model. Koblan et al. used the clinical adeno-associated virus vector for co-packaged ABEmax-VRQR to make the correction of mutation in many tissues, but not all, in mouse model, resulting in improved vascular pathology and extended the HGPS mice lifespan
