Liver-Targeted AAV8 Gene Therapy Ameliorates Skeletal and Cardiovascular Pathology in a Mucopolysaccharidosis IVA Murine Model.

ABSTRACT: Mucopolysaccharidosis type IVA (MPS IVA) is due to the deficiency of GALNS (N-acetylgalactosamine 6-sulfate sulfatase) and is characterized by systemic skeletal dysplasia. We have evaluated adeno-associated virus 8 (AAV8) vectors expressing different forms of human GALNS under a liver-specific promoter. The vectors were delivered intravenously into 4-week-old MPS IVA knockout (KO) and immune tolerant (MTOL) mice at a dose of 5 × 10¹³ genome copies (GC)/kg. These mice were monitored for 12 weeks post-injection. GALNS enzyme activity was elevated significantly in plasma of all treated mice at 2 weeks post-injection. The activity observed was 4- to 19-fold higher than that in wild-type mice and was maintained throughout the monitoring period. Treatment with AAV vectors resul

SUBMITTER: Sawamoto K 

PROVIDER: S-EPMC7301175 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature