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DOTAP (and other cationic lipids): chemistry, biophysics, and transfection.

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Laboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.


Cationic lipid-mediated nucleic acid and protein delivery is becoming increasingly popular for in vitro and in vivo applications. While the chemistry of cationic lipid carriers is moving very rapidly, and more and more sophisticated molecules are being developed, it is worthwhile to look back to understand what has been achieved in the field of cationic lipids and why in some cases delivery based on cationic lipids works and in other cases it does not. For this purpose, DOTAP is one of the best candidates; it is the most widely used cationic lipid, it is relatively cheap, and it is efficient in both in vitro and in vivo applications. The vast amount of data that have accumulated on DOTAP and related molecules could provide invaluable clues to biophysical, structural, and biological mechanisms of transfection by cationic lipids. While many issues of cationic lipid transfection still remain unclear, this review will attempt to address mainly the following issues: (1) interplay of physicochemical parameters of DOTAP formulations; (2) impact of physicochemical parameters on transfection (lipofection) efficiency by cationic reagents, in vitro and in vivo; (3) structure-activity relationships of cationic lipid formulations in cell culture and in the living organism. In addition, in vivo applications of cationic lipids are reviewed, and the problems of local versus systemic administration of lipoplexes are discussed.

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