Gene therapy directed to the gastroenterological manifestations of cystic fibrosis (CF) would ideally be administered systemically. Such delivery would require efficient targeting at the cellular level to achieve a safe and effective therapy. Here we describe gene delivery using the secretin receptor (SR) as a basolateral target specific to the biliary and pancreatic epithelia affected in CF patients. We describe here targeting of a polycation-based nonviral gene delivery vector and retargeting of an adenoviral vector to cells expressing the SR in vitro. We were able to transfect cells expressing the SR up to 10-fold more efficiently than those not expressing the SR with a targeted polycation, SecGGC-IPEI. This targeting effect was secretin-specific and substantially reduced by competing secretin. SR-retargeted adenovirus transduced SR-expressing cells at more than six-fold higher levels than adenovirus alone. The SR may be an effective target for targeting systemically applied viral and nonviral gene delivery constructs to disease-affected tissues in CF patients.
- Cystic fibrosis
- Secretin receptor