TRANSIENT IMMUNOSUPPRESSION ALLOWS TRANSGENE EXPRESSION FOLLOWING READMINISTRATION OF ADENOASSOCIATED VIRAL VECTORS

Adeno-associated viral (AAV) vectors have much promise in gene therapy , Among the many properties that make AAV an ideal vector for gene the rapy are its ability to infect both dividing and nondividing cells and the longevity of expression in tissues such as brain, skeletal muscle , and liver, However, like other viral vectors, readministration of ve ctor is limited because of the host's immune response to viral compone nts of the vector, Using class I, class II, and CD40 ligand (CD40L)-de ficient mice, we demonstrate that neutralizing antibodies to the viral capsid proteins prevent transgene expression following readministrati on of rAAV vectors, Transient immunosuppression of mice by treatment w ith antibody to CD4 at the time of primary infection allowed transgene expression after readministration of rAAV vectors to animals, Transie nt immunosuppression with antibody to CD40L had only a modest effect o n the efficacy of readministration, The ability to readminister virus was inversely correlated with both AAV capsid enzyme-linked immunosorb ent assay titers and AAV neutralizing antibody titers, These studies d emonstrate that readministration of rAAV can be accomplished by down r egulating the anti-AAV immune response and suggest the use of repeated administration of rAAV as a viable form of therapy for the treatment of chronic diseases.