PURPOSE: Biolabile cationic lipids were developed for efficient intracellular delivery of DNA and siRNA. METHODS: The compounds have been designed starting from the membrane lipid DOPC in a way they may loose their cationic charge when exposed to an acidic and/or enzymatic stimulus, such as those met during the journey of a lipoplex in biological media. RESULTS: They demonstrated remarkable efficiency to deliver DNA in various cell lines (BHK-21, Calu-3, NCI-H292, and A549), with no significant cytotoxicity. Furthermore, two of the compounds (carbonate-based DOPC derivatives) revealed able to deliver small interfering RNA in U87Luc and A549Luc cancer cells and to mediate a selective 70-80% knockdown of the stably transfected luciferase gene. CONCLUSIONS: The results show that the described bioresponsive cationic lipids have high DNA and siARN delivery activity which is encouraging in view of delivering a therapeutic nucleic acid to pulmonary tissues in vivo.
PURPOSE: Biolabile cationic lipids were developed for efficient intracellular delivery of DNA and siRNA. METHODS: The compounds have been designed starting from the membrane lipidDOPC in a way they may loose their cationic charge when exposed to an acidic and/or enzymatic stimulus, such as those met during the journey of a lipoplex in biological media. RESULTS: They demonstrated remarkable efficiency to deliver DNA in various cell lines (BHK-21, Calu-3, NCI-H292, and A549), with no significant cytotoxicity. Furthermore, two of the compounds (carbonate-based DOPC derivatives) revealed able to deliver small interfering RNA in U87Luc and A549Luc cancer cells and to mediate a selective 70-80% knockdown of the stably transfected luciferase gene. CONCLUSIONS: The results show that the described bioresponsive cationic lipids have high DNA and siARN delivery activity which is encouraging in view of delivering a therapeutic nucleic acid to pulmonary tissues in vivo.
Authors: R C MacDonald; G W Ashley; M M Shida; V A Rakhmanova; Y S Tarahovsky; D P Pantazatos; M T Kennedy; E V Pozharski; K A Baker; R D Jones; H S Rosenzweig; K L Choi; R Qiu; T J McIntosh Journal: Biophys J Date: 1999-11 Impact factor: 4.033
Authors: J Rosenecker; S Naundorf; S W Gersting; R W Hauck; A Gessner; P Nicklaus; R H Müller; C Rudolph Journal: J Gene Med Date: 2003-01 Impact factor: 4.565