Evaluation of viral sensitizer-mediated enhancement of AAV transduction in vivo
Gene therapy has the potential to cure a wide range of debilitating genetic diseases. One of the best ways to correct a genetic defect is to use a viral vector to deliver a functional copy of the gene to cells in the body so that they can express a functional protein and reverse the disease phenotype. Currently, adeno-associated virus (AAV) vectors are the leading gene delivery platforms as they can infect almost any cell type in the body and can elicit sustained expression of a function protein. While highly effective, some genetic diseases, like spinal muscular atrophy (SMA), require very high doses of AAV to be administered to the patients in order to reach all the necessary target cells. High doses of AAV, as well as pre-existing immunity to AAV, have been associated with toxicities. The objective of this proposal is to evaluate whether vector potentiators (VEPOs) identified by Virano Therapeutics can be administered at the time of AAV delivery to improve the efficiency of AAV transduction, thereby permitting the administration of lower doses of AAV to achieve the same therapeutic efficacy.