538. Functional Correction of A-T Cells by ATM Gene Expression Mediated by HSV Amplicon Vector after the Ionizing Radiation or under Oxidative Stress Condition

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Ataxia-telangiectasia (A-T) is a progressive degenerative autosomal recessive disease characterized by ataxia, telangiectases, immune dysfunction, cancer predisposition, and sensitivity to ionzing radiation. Presently, there is no treatment to slow the clinical progression of A-T, or improve A-T cell function. Therefore individuals with A-T receive supportive treatment only. For this reason, gene therapy, particularly for the organs effected in A-T (i.e. the cerebellum and hematopoietic cells), is being considered as a therapeutic measure for treating A-T patients. Previously, we employed a Herpes simplex viral (HSV) amplicon vector (pTO-ATM) to transfer the ATM gene into both the ATM-deficient AT22 cell line and into rat brains, and demonstrated functional expression of the ATM gene. In this study, we will present the functional restoration of the normal phenotype, as ATM gene transfer resulted in increased resistance to oxidative stress and ionizing radiation in cultured primary A-T cells, as measured by the colony forming-efficiency assay. These studies should lay important groundwork for furthering gene therapy approaches for A-T patients.