Cationic liposome-mediated gene transfer to rat salivary epithelial cells in vitro and in vivo

Background Previously we have shown that gene transfer to salivary gland ep ithelial cells readily occurs via recombinant adenoviruses, although the re sponse is short-lived and results in a potent host immune response. The aim of the present study was to assess the feasibility of using cationic lipos omes to mediate gene transfer to rat salivary cells in vitro and in vivo. Methods Initially, for transfection in vitro, we used two cationic liposome formulations (GAP-DLRIE/DOPE and DOSPA/DOPE) complexed with plasmid encodi ng human growth hormone (hGH) as a reporter gene. Thereafter, using GAP-DLR IE/DOPE, plasmids were transferred to rat salivary glands in vivo, and hGH levels measured in saliva, serum and gland extracts. Results Under optimal conditions, transfection of rat submandibular glands (SMGs) was consistently observed. Approximately 95% of the cells transfecte d with a plasmid encoding beta -galactosidase were acinar cells. Maximal hG H expression was obtained during the first 48 h post-transfection using a p lasmid encoding the hGH cDNA and complexed with GAP-DLRIE/ DOPE. hGH was de tected in gland extracts and saliva, and occasionally in serum. No systemic or local gland pathology was consistently or significantly observed. Conclusions The levels of the reporter gene product, hGH, obtained after GA P-DLRIE/DOPE-mediated gene transfer are considerably lower (<0.5%) than tho se achieved with adenoviral vectors (10(8) PFU). Nonetheless, cationic lipo some-mediated gene transfer to salivary glands may be useful for potential therapeutic applications. Copyright (C) 2000 John Wiley & Sons, Ltd.