Premium
Nature of linkage between the cationic headgroup and cholesteryl skeleton controls gene transfection efficiency
Author(s) -
Ghosh Yamuna Krishnan,
Visweswariah Sandhya S.,
Bhattacharya Santanu
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01558-1
Subject(s) - transfection , lipofectamine , chemistry , cationic polymerization , liposome , cationic liposome , amphiphile , gene delivery , ether , bromide , reagent , ammonium bromide , combinatorial chemistry , stereochemistry , biochemistry , organic chemistry , gene , pulmonary surfactant , copolymer , recombinant dna , vector (molecular biology) , polymer
Three novel cationic cholesterol derivatives with different modes of linkage between the cationic headgroup and the cholesteryl backbone have been synthesized and used as mixtures with 1,2‐dioleoyl‐ L ‐α‐glycero‐3‐phosphatidyl ethanolamine (DOPE) for liposome‐mediated gene transfection. A pronounced improvement in gene transfer efficiency was observed when the cationic center was appended to the cholesteryl backbone using an ether linkage as opposed to when the linkages were based on either ester or urethane groups. Amphiphiles with ether links such as cholest‐5‐en‐3β‐oxyethane‐ N , N , N ‐trimethyl ammonium bromide (2) and cholest‐5‐en‐3β‐oxyethane‐ N , N ‐dimethyl‐ N ‐2‐hydroxyethyl ammonium bromide (3) showed transfection efficiencies considerably greater than commercially available gene transfer reagents. Notably, the transfection ability of 2 with DOPE in the presence of serum was significantly greater than Lipofectamine ® and Lipofectin ® . Interestingly, 3 did not require the helper lipid DOPE for transfection. This suggests that these newly described cholesterol‐based amphiphiles should be very promising in liposome‐mediated gene transfection. The advantage that the ether linkage possesses would be important in the design of newer, more efficient cholesterol‐based delivery reagents.