Advances of adeno-associated virus applied in gene therapy to hemophilia from bench work to the clinical use

• Main Authors: Xiaolei Pei, Mingzhe Han, Lei Zhang
• Format: Article
• Language: English
• Published: Wolters Kluwer Health 2019-10-01
• Series: Blood Science
• Online Access: http://journals.lww.com/10.1097/BS9.0000000000000030

Abstract. Hemophilia A and B are diseases caused by a single gene deficiency and are thus suitable for gene therapy. In recent clinical research, adeno-associated virus (AAV) was employed by several teams in the treatment of hemophilia A and B, and the outcomes were encouraging. In this review, we summarized the most recent research on the mechanism and application of AAV in the treatment of hemophilia, trying to analyze the advantages of AAV gene therapy and the main challenges in its clinical use. We also summarized the clinical trials involving hemophilia, especially those employing AAV gene therapy to treat hemophilia A and B, some of which have already been completed and some that are still ongoing. From the reports of the completed clinical trials, we tried to determine the correlations among AAV dose, AAV serotype, immune response, and gene expression time. Finally, taking into account the most recent studies investigating AAV capsid modification, transgene optimization, and AAV chaperones, we summarized the direction of basic research and clinical applications of AAV in the future.