title: Enhanced intravenous transgene expression in mouse lung using cyclic-head cationic lipids.
abstract: 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.
authors.affiliation: Division of Lipid Science and Technology, Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Bharat Kumar
authors.initials: BK
authors.lastname: Majeti
authors.forename: Rajkumar Sunil
authors.initials: RS
authors.lastname: Singh
authors.forename: Sudheer Kumar
authors.initials: SK
authors.lastname: Yadav
authors.forename: Surendar Reddy
authors.initials: SR
authors.lastname: Bathula
authors.forename: Sistla
authors.initials: S
authors.lastname: Ramakrishna
authors.forename: Prakash Vamanrao
authors.initials: PV
authors.lastname: Diwan
authors.forename: Surkara Sakunthala
authors.initials: SS
authors.lastname: Madhavendra
authors.forename: Arabinda
authors.initials: A
authors.lastname: Chaudhuri
mesh_terms: 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*
chemical_list: D008055:Lipids; D008081:Liposomes; D004247:DNA