Gene Transfer to the Salivary Glands: Applications in Gene Therapy

Transfer of genetic material to salivary glands offers a wide range of potential clinical applications, such as correction of salivary function (Mastrangeli et al.,1994), therapy of salivary carcinomas (Samuelson, 1996) and secretion of therapeutic proteins such as growth factors, enzymes and antigens (Barka, 1996). The salivary glands hold several advantages for gene transfer: salivary cells are designed to synthesize and secrete abundant quantities of proteins both to the saliva and the blood circulation. In addition, salivary glands are readily accessible without surgery by cannulation via their excretory duct, which open in the mouth. In humans, salivary glands are routinely cannulized for contrast imagining (Baum, 1999). Salivary glands are comprised of acinar cells and ductal cells (Figure 1). The acinar cells synthesize most of the exocrine proteins in the saliva and the ductal cells carry the saliva to the oral cavity and control its electrolyte composition. In addition to their essential roles in proper maintenance of the upper digestive system by exocrine secretion, salivary secreted endocrine proteins have been reported to affect distal tissues. Salivary proteins such as epidermal growth factor (EGF), nerve growth factor (NGF) (Arancibia, 1985), renin and kalikreins (Penschow, 1993) were traced in the blood circulation. NGF was also traced in the nerve system (Arancibia, 1985).