Enhanced intravenous transgene expression in mouse lung using cyclic-head cationic lipids.
Herein, we report enhanced intravenous mouse lung transfection using novel cyclic-head-group analogs of usually open-head cationic transfection lipids. Design and synthesis of the new cyclic-head lipid N,N-di-n-tetradecyl-3,4-dihydroxy-pyrrolidinium chloride (lipid 1) and its higher alkyl-chain analogs (lipids 2-4) and relative in vitro and in vivo gene transfer efficacies of cyclic-head lipids 1-4 to their corresponding open-head analogs [lipid 5, namely N,N-di-n-tetradecyl-N,N-(2-hydroxyethyl)ammonium chloride and its higher alkyl-chain analogs, lipids 6-8] have been described. In stark contrast to comparable in vitro transfection efficacies of both the cyclic- and open-head lipids, lipids 1-4 with cyclic heads were found to be significantly more efficient (by 5- to 11-fold) in transfecting mouse lung than their corresponding open-head analogs (5-8) upon intravenous administration. The cyclic-head lipid 3 with di-stearyl hydrophobic tail was found to be the most promising for future applications.
Majeti
Bharat Kumar
BK
Division of Lipid Science and Technology, Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Singh
Rajkumar Sunil
RS
Yadav
Sudheer Kumar
SK
Bathula
Surendar Reddy
SR
Ramakrishna
Sistla
S
Diwan
Prakash Vamanrao
PV
Madhavendra
Surkara Sakunthala
SS
Chaudhuri
Arabinda
A
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry; D008081:Liposomes / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014162:Transfection / Q000379:methods; D019076:Transgenes / Q000235:genetics*
D008055:Lipids; D008081:Liposomes; D004247:DNA