Use of Mesenchymal Stem Cells to Enhance the Efficacy of Gene Therapy.

Herein, a method to use of mesenchymal stem cells (MSCs) to modulate immune response against rAAV transduction in a canine Duchenne muscular dystrophy (DMD) model is presented. The aim is to overcome the immune response against adeno-associated virus (AAV) capsid itself as well as against the AAV-derived transgene.AAV is currently the most used viral vector because of its relative safety and high efficiency of gene transfer to nondividing cells. Since DMD is caused by a deficiency of dystrophin protein due to mutation or deletion in the dystrophin gene, dystrophin replacement therapy using AAV vectors carrying dystrophin as a therapeutic gene is an effective treatment as shown by animal experiments and clinical trials. Because DMD is a systemic disease, the amount of AAV vector required to achieve efficacy is impractically large. MSC have been used in combination with organ transplants due to their immunomodulatory effects. By using MSCs and AAVs in combination as described below, we are able to decrease the immune response to AAV capsid and the transgene as well as to reduce the dose of AAV to approximately 1/100 of the dose used in conventional clinical trials.