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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Secretin-mediated gene delivery, a specific targeting mechanism with potential for treatment of biliary and pancreatic disease in cystic fibrosis.

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-lPEI. This targeting effect was secretin-specific and substantially reduced by competing secretin. SR-retargeted adenovirus transduced SR-expressing cells at more than sixfold 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.[1]


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