High Efficiency of Transfection Agents Using Bio-Compatable PH Cleavable Linkers
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Abstract
Transfection agents were synthesis using solid phase chemistry and utilizing a pH cleavable linker. These compounds are based on 3-Amino-1, 2-propanediol and polyamine conjugate (spermine) to a steroid or bile acids. To optimize the transfection efficiency a series of structure-activity relationship studies were carried out by altering the steroid or fatty acid by systematic variation of the acid chain length. We demonstrate that transfection activity of our compound formulated with DOPE as a co lipid is comparable with commercial available, DC-Chol, transfectam, DOTAP and ESCORTTM respectively. This result suggests our bile acid based cationic lipid is more effective than those commercially available. The most potent compound was N1-(3α,7α-dihydroxy-5β-cholan-24-carbonyl)-1,12-diamino-4,9-diazadecane.
Keywords: Transfection agents, gene therapy, solid phase chemistry, safety-catch linker, pH cleavable linker, liposome, pEGFPLuc plasmid DNA.
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