AAV-G6PC genome editing therapy

AAV-G6PC genome editing therapy is an academic, preclinical liver-directed CRISPR-based gene-editing approach for glycogen storage disease type Ia. It uses two adeno-associated virus vectors: a CRISPR vector encoding Streptococcus pyogenes Cas9 and a donor vector carrying a guide RNA plus a therapeutic G6PC transgene. Cas9-mediated cleavage at the endogenous G6PC locus enables homology-directed chromosomal insertion of the donor transgene, aiming to restore durable hepatocyte expression of glucose-6-phosphatase-alpha and avoid the progressive loss of episomal AAV genomes during liver growth. The approach has produced metabolic correction in murine and canine GSD Ia models but has not been identified as a named clinical product or an active human clinical program. (insight.jci.org)