Expression of human tissue kallikrein in rat salivary glands and its secretion into circulation following adenovirus-mediated gene transfer.

Replication-deficient adenovirus Ad.CMV-cHK, expressing human tissue kallikrein under the control of the cytomegalovirus enhancer/promoter, was introduced into rat salivary glands via a direct intracapsular injection. A single injection of Ad.CMV-cHK at a dose of 4 x 10(9) pfu resulted in a sustained expression of human tissue kallikrein in rat salivary glands. The level of immunoreactive human tissue kallikrein in rat sera was the highest at 1 day post gene delivery when both salivary glands were injected and decreased in a time-dependent manner after gene delivery. Human tissue kallikrein levels in sera increased concomitantly with the amount of adenovirus used in direct salivary injection. The detection of human tissue kallikrein in sera after gene delivery into salivary glands provided direct evidence indicating that rat salivary glands secrete locally synthesized human tissue kallikrein to the systemic circulation. The direct injection of salivary glands with replication-deficient adenovirus could provide a systemic route for gene delivery for studying salivary gland function and development. Targeted gene delivery to the salivary gland may provide the means to express therapeutic proteins in saliva and the systemic circulation.