552. Transduction of Salivary Gland Acinar Cells in Rodents with Adeno Associated Viral Vectors Results in Persistent Exocrine and Endocrine Release of Recombinant Proteins

Abstract

Salivary glands are secretory epithelial organs in the mouth that are important in oral health. Disorders affecting salivary glands such as Sjogren's syndrome and damage following radiation therapy for head and neck cancer result in significant lifestyle changes and oral discomfort in patients. Gene transfer studies to the salivary glands for therapeutic or physiology studies have been hampered by a lack of vectors for efficient long-term transduction of acinar cells within the gland. By using a combination of approaches we have identified AAV isolates able to efficiently transduce acinar cells. Membrane-Tomato floxed membrane-GFP transgenic mice in combination with AAV encoded CMV-CRE recombinase expression cassette were used to rapidly identify serotypes able to transduced acinar cells. Biodistribution beyond the salivary gland was measured using vectors encoding firefly luciferase and xenogen imaging. In order to study the secretory properties of transduced acinar cells we cannulated mouse parotid glands with AAV vectors encoding Gaussia Luciferase or recombinant parathyroid hormone containing a nerve growth factor signal peptide. We could observe that both proteins can be detected in blood and saliva for at least 1 month post cannulation. Moreover the ratio blood/saliva secretion could be altered by treatment with pilocarpine or isoproterenol offering a unique mechanism for regulating the release of recombinant proteins in the salivary gland.