PRODUCE/TEST ADENOVIRUS VECTORS FOR CLINICAL USE

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Salivary hypofunction that follows the loss of acinar cells is debilitating for patients and tends to be progressive and irreversible. This type of hypofunction is typical of patients who have had therapeutic radiation involving the glands, or patients with Sjogren's syndrome. One approach to this clinical problem is to increase the water-secreting capacity of the cells that remain in diseased glands. Candidate proteins for this function have been identified (aquaporins), and preclinical data suggest that the aquaporins may be useful in improving the function of radiated salivary glands. On the other hand, normal salivery glands may secrete therapeutic proteins for disorders of the oral and pharyngeal tissues. For example, antimicrobial proteins might be secreted in the saliva for the treatment of mucosal infections. In either case, these strategies depend on the efficient transfer of the exogenous gene to the salivary glands. For this purpose, adenovirus-based vectors are the best available candidates for salivary gland gene transfer. The purpose of this project is to produce clinical grade adenovirus vectors for use in the salivary glands, as part of Phase I clinical trials. The production of adenovirus vectors for clinical applications requires specialized knowledge, considerable skill, and dedicated facilities.