Enhanced intravenous transgene expression in mouse lung using cyclic-head cationic lipids |
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Authors: | Majeti Bharat Kumar Singh Rajkumar Sunil Yadav Sudheer Kumar Bathula Surendar Reddy Ramakrishna Sistla Diwan Prakash Vamanrao Madhavendra Surkara Sakunthala Chaudhuri Arabinda |
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Institution: | Division of Lipid Science and Technology, Indian Institute of Chemical Technology, Hyderabad 500 007, India. |
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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. |
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