Abstract
Top of pageAbstract Targeted delivery of functional oligonucleotides to pulmonary endothelium shows promise both as a novel therapeutics for the treatment of pulmonary diseases and as a research tool to study gene function in pulmonary endothelium. To this end, we have developed a novel lipidic vector that is highly efficient in targeted delivery to pulmonary endothelium of functional oligonucleotides including antisense ODN, siRNA and synthetic minigenes. This is based on a method that utilizes an ionizable aminolipid (1,2-dioleoyl-3-dimethylammonium propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities of polyanionic ODN in lipid vesicles. An endothelium-specific antibody (34A) is incorporated into the lipid vesicles via a distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) spacer. These vesicles are around 100-200 nm in diameter with an ODN entrapment efficiency of 60-80%. 34A antibody mediated efficient delivery of ODN to mouse lung endothelial cells in vitro and in intact mice. Furthermore, this formulation is associated with minimal proinflammatory cytokine response and other hematological toxicities. These results provide a basis for lipid-mediated delivery of ODN for the treatment of pulmonary diseases. They also suggest the utility of this approach as a research tool to characterize the function of genes in the pulmonary endothelium.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
