Retrovirus-Mediated Gene Transfer into Salivary Glands In Vivo

In the present report, we show prolonged expression of β-galactosidase (β-Gal) in the acinar cells of the submandibular and sublingual glands of rats following retrograde ductal injection of the retroviral vector BAG. To facilitate integration of viral DNA, cell division in the gland was induced by the administration of the β-adrenergic agonist isoproterenol prior to the delivery of the vector. The frequency of cells stained for β-Gal was higher if the virus was injected 4–20 hr after the two injections of isoproterenol given 24 hr apart than after the injection of only one dose of the drug. Without stimulation of cell division, no integration of the viral DNA was observed. Expression of the marker enzyme was observed up to 43 days, the limit of the observation period. The data indicate that salivary glands are potential targets of retrovirus-mediated gene transfer for somatic gene therapy. The major salivary glands would be attractive targets of somatic gene therapy because viral vectors can be transferred to duct and acinar cells by simple and relatively harmless retrograde ductal injections. We show here the prolonged expression of β-galactosidase (β-Gal) in acinar cells following retrovirus-mediated gene transfer into the salivary glands of rats in which cell replication is stimulated by the administration of the β-adrenergic agonist isoproterenol.