Muscle Gene Therapy for HemophiliaDenise E. Sabatino1,2 and Valder R. Arruda1,2*
- *Corresponding Author:
- Valder R. Arruda
The Children’s Hospital of Philadelphia
3501 Civic Center Boulevard
5056 Colket Translational Research Center
Philadelphia, PA 19194, USA
E-mail: [email protected]
Received date: February 11, 2012; Accepted date:May 07, 2012; Published date: May 07, 2012
Citation: Sabatino DE, Arruda VR (2012) Muscle Gene Therapy for Hemophilia. J Genet Syndr Gene Ther S1:010. doi:10.4172/2157-7412.S1-010
Copyright: © 2012 Sabatino DE, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Muscle-directed gene therapy for hemophilia is an attractive strategy for expression of therapeutic levels of clotting factor as evident from preclinical studies and an early phase clinical trial. Notably, local FIX expression by AAV-mediated direct intramuscular injection to skeletal muscle persists for years. Development of intravascular delivery of AAV vector approaches to skeletal muscle resulted in vector in widespread areas of the limb and increased expression of FIX in hemophilia B dogs. The use of FIX variants with improved biological activity may provide the opportunity to increase the efficacy of these approaches. Studies for hemophilia A are less developed at this point, but utilizing transgenes that improve hemostasis independent of FIX and FVIII has potential therapeutic application for both hemophilia A and B. Continuous monitoring of humoral and T cell responses to the transgene and AAV capsid in human trials will be critical for the translation of these promising approaches for muscle gene therapy for hemophilia.