Preclinical Studies:

1. Gene Therapy for Alpha-1 Antitrypsin Deficiency: In a mouse model of alpha-1 antitrypsin deficiency, researchers used adeno-associated virus (AAV) vectors to deliver a normal copy of the SERPINA1 gene to the liver, resulting in increased production of the alpha-1 antitrypsin protein and a decrease in liver damage.
2. CRISPR/Cas9 for Hereditary Tyrosinemia Type I: A study used AAV vectors to deliver the CRISPR/Cas9 system to the livers of mice with hereditary tyrosinemia type I, a genetic disease that affects the liver. They were able to correct the genetic mutation that causes the disease, demonstrating the potential of this approach for treating genetic liver diseases.

Clinical Studies:

1. Gene Therapy for Hemophilia B: A phase 1/2 clinical trial used an AAV vector to deliver a normal copy of the F9 gene, which is mutated in hemophilia B, to the livers of patients with the disease. The therapy led to sustained increases in clotting factor IX activity, reducing the frequency of bleeding episodes.
2. Gene Therapy for Hemophilia A: BioMarin Pharmaceutical’s valoctocogene roxaparvovec (Roctavian), an AAV vector-based gene therapy for hemophilia A, showed promising results in a Phase 3 clinical trial. The trial demonstrated that a single administration of the gene therapy could maintain therapeutic levels of factor VIII, the clotting factor that is missing or deficient in patients with Hemophilia A.
3. Gene Therapy for Alpha-1 Antitrypsin Deficiency: A clinical trial used an AAV vector to deliver a normal copy of the SERPINA1 gene to the livers of patients with alpha-1 antitrypsin deficiency. The therapy was well-tolerated and led to an increase in circulating alpha-1 antitrypsin levels.