title: Alkane-modified short polyethyleneimine for siRNA delivery.
abstract: RNA interference (RNAi) is a highly specific gene-silencing mechanism triggered by small interfering RNA (siRNA). Effective intracellular delivery requires the development of potent siRNA carriers. Here, we describe the synthesis and screening of a series of siRNA delivery materials. Short polyethyleneimine (PEI, Mw 600) was selected as a cationic backbone to which lipid tails were conjugated at various levels of saturation. In solution these polymer-lipid hybrids self-assemble to form nanoparticles capable of complexing siRNA. The complexes silence genes specifically and with low cytotoxicity. The efficiency of gene knockdown increased as the number of lipid tails conjugated to the PEI backbone increased. This is explained by reducing the binding affinity between the siRNA strands to the complex, thereby enabling siRNA release after cellular internalization. These results highlight the importance of complexation strength when designing siRNA delivery materials.
authors.affiliation: Department of Chemical, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Avi
authors.initials: A
authors.lastname: Schroeder
authors.forename: James E
authors.initials: JE
authors.lastname: Dahlman
authors.forename: Gaurav
authors.initials: G
authors.lastname: Sahay
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Love
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Eltoukhy
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Levins
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Wang
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000473:Alkanes / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D049409:Luciferases, Firefly / Q000235:genetics; D049410:Luciferases, Renilla / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D013499:Surface Properties; D014162:Transfection
chemical_list: D000473:Alkanes; D004337:Drug Carriers; D008055:Lipids; D034741:RNA, Small Interfering; D011094:Polyethyleneimine; D049410:Luciferases, Renilla; D049409:Luciferases, Firefly