Neutralizing antibodies against adeno-associated viruses in @entity29 XXXX : implications for gene therapy.

@entity1 @entity31 @entity29 @entity8787 @entity30
BACKGROUND: @entity29 ( @entity29 ) are comprised of two major disorders: @entity30 ( @entity30 ) and @entity31 ( @entity31 ). No curative treatment options are available, but gene therapy may offer an alternative therapeutic approach. For this a safe and reliable vector is needed. The adeno-associated viruses (AAV) have attracted considerable interest as gene therapy vectors. However, neutralizing antibodies (nAb's) made in response to wildtype AAV have been associated with a partial to complete block of transduction in case of reexposure. Therefore, and in order to define AAV vector candidates to treat @entity8787 @entity1 , we characterized preexisting humoral responses to AAV in this population. METHODS: We measured circulating antibodies against AAV serotypes 1, 2, 3, 4, 5, 6, and 8 using a previously established virus neutralization assay. In all, 100 healthy donors and 200 @entity8787 patient's serum samples (101 @entity30 and 99 @entity31 ) were analyzed. RESULTS: A significant difference was detected in the prevalence of nAb's for AAV types 1, 5, 6, and 8 between the healthy donors and the @entity1 population. Furthermore, various disease phenotypic characteristics correlated with the prevalence of nAb's to all the serotypes studied. CONCLUSIONS: Our study establishes a foundation for the development of an AAV-based gene therapy approach as a novel treatment for @entity8787 . Furthermore, we show a relationship between disease phenotype in @entity8787 @entity1 and the humoral immune response to AAV.
