Preclinical pharmacology and toxicology study of an AAV8-tATP7B vector for Wilson's disease - PubMed
3 days ago
- #Gene Therapy
- #AAV8 Vector
- #Wilson's Disease
- Study focuses on developing a novel gene therapy for Wilson's disease (WD) using an AAV8-tATP7B vector.
- Codon-optimized full-length or truncated ATP7B (tATP7B) genes were used with liver-specific mini promoters in the AAV8 vector.
- Truncated ATP7B showed comparable copper export ability but higher expression efficiency than full-length ATP7B in HepG2 cells.
- AAV8-tATP7B restored copper homeostasis and liver function in Atp7b-/- mice in a dose-dependent manner over 24 weeks.
- Toxicity studies in rats and monkeys showed no systemic toxicity, with reversible liver changes in monkeys at high doses.
- 6×10¹³ vg/kg was established as the maximum tolerated dose based on the toxicity studies.
- The study concludes that AAV8-tATP7B is effective and safe, supporting its clinical translation for WD patients.