Gene Therapy for Hemophilia A

To the Editor: Ozelo et al. (March 17 issue)(1) report the results of a phase 3 trial of an adeno-associated virus 5 (AAV5)-based gene-therapy vector in men with severe hemophilia A. However, in a murine model, AAV5 vectors were found to transduce primary human hepatocytes inefficiently.(2) Forced expression of factor VIII in hepatocytes leads to a cellular stress response,(3) which may have played a role in the progressive decline in factor VIII levels over time in a phase 1-2 trial of the same vector. In the current trial, the dose of AAV5 (6x10(13) vector genomes per kilogram of body weight) . . .

Automated summary

This study reports the results of a gene therapy trial for severe hemophilia A. The low transduction efficiency of AAV5 vector and the stress response in hepatocytes may contribute to the decline in factor VIII levels.