Preclinical development of TAK-754, a high-performance AAV8-based vector expressing coagulation factor VIII.

ABSTRACT: This report concerns the preclinical development of TAK-754, an AAV8-based human factor VIII (FVIII) vector designed to deliver a codon-optimized and CpG-depleted B domain-deleted F8 transgene under the control of a liver-specific promoter for gene therapy in patients with hemophilia A. A dose-dependent increase in plasma FVIII activity was detected in FVIII knockout mice at a dose of 1.0 × 10¹² TAK-754 capsid particles (CP)/kg or higher. This increase was shown to be in accordance with a dose-dependent decrease in blood loss in a hemostatic efficacy assay. TAK-754 (3.1 × 10¹² CP/kg) mediated long-term and stable FVIII expression in immunologically tolerant transgenic human FVIII mice. Toxicology and biodistribution assessments with a single administration of T

SUBMITTER: Lengler J 

PROVIDER: S-EPMC11929063 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature