Efficacious genome editing in infant mice with glycogen storage disease type Ia.

ABSTRACT: Glycogen storage disease type Ia (GSD Ia) is caused by a deficiency of glucose-6-phosphatase (G6Pase) in the liver leading to lethal hypoglycemia. Gene therapy with adeno-associated virus (AAV) vectors encoding G6Pase fails to stably treat GSD Ia early in life. We evaluated genome editing in 12-day-old infant mice with GSD Ia using 2 AAV vectors, one containing Cas9 from Streptococcus pyogenes and a second Donor vector that expresses a guide RNA and a G6PC transgene. Gene therapy with the Donor vector only was compared with genome editing using both Donor and CRISPR vectors. Treatment with genome editing (total vector dose 0.2 × 1013 to 2 × 1013 vector genomes/kg) and bezafibrate (to stimulate autophagy) was efficacious, as assessed by hypoglycemia prevention and the frequency of transgene

SUBMITTER: Arnson B 

PROVIDER: S-EPMC12487852 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature