Tripod-like cationic lipids as novel gene carriers.
An innovative family of tridentate-cationic "single-chained lipids" designed to enhance DNA compaction and to promote endosomal escape was synthesized by coupling various lipids to a multibranched scaffold. DNA retardation assays confirmed the ability of the most members of the library to complex DNA. Classical molecular dynamics simulations performed on the lauryl derivative, bound to a short strand of DNA in aqueous solution supported these observations. These showed that two "arms" of the tripodal molecule are ideally suited to forming strong Coulombic interactions with two contiguous phosphate groups from the DNA backbone while the lipophilic tail stays perpendicular to the DNA helix. Gene transfer abilities of the library were assessed in multiple cell lines (CHO, Cos7, and 16HBE14o-) with some library members giving excellent transfection abilities and low cytotoxicity, supporting the use of this tripodal approach for the development of efficient gene delivery agents.
Unciti-Broceta
Asier
A
School of Chemistry, West Mains Road, University of Edinburgh, UK.
Holder
Emma
E
Jones
Lisa J
LJ
Stevenson
Barbara
B
Turner
Andrew R
AR
Porteous
David J
DJ
Boyd
A Chris
AC
Bradley
Mark
M
D000818:Animals; D002412:Cations; D002460:Cell Line; D004247:DNA / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D008055:Lipids / Q000737:chemistry*
D002412:Cations; D008055:Lipids; D004247:DNA