title: A peptidomimetic siRNA transfection reagent for highly effective gene silencing.
abstract: RNA interference (RNAi) techniques hold forth great promise for therapeutic silencing of deleterious genes. However, clinical applications of RNAi require the development of safe and efficient methods for intracellular delivery of small interfering RNA (siRNA) oligonucleotides specific to targeted genes. We describe the use of a lipitoid, a cationic oligopeptoid-phospholipid conjugate, for non-viral transfection of synthetic siRNA oligos in cell culture. This peptidomimetic delivery vehicle allows for efficient siRNA transfection in a variety of human cell lines with negligible toxicity and promotes extensive downregulation of the targeted genes at both the protein and the mRNA level. We compare the lipitoid reagent to a standard commercial transfection reagent. The lipitoid is highly efficient even in primary IMR-90 human lung fibroblasts in which other commercial reagents are typically ineffective.
authors.affiliation: Department of Chemistry, New York University, New York, NY 10003, USA.
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Utku
authors.forename: Elinor
authors.initials: E
authors.lastname: Dehan
authors.forename: Ouathek
authors.initials: O
authors.lastname: Ouerfelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Piano
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Zuckermann
authors.forename: Michele
authors.initials: M
authors.lastname: Pagano
authors.forename: Kent
authors.initials: K
authors.lastname: Kirshenbaum
mesh_terms: D002412:Cations; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008055:Lipids; D008081:Liposomes; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D010714:Phosphatidylethanolamines / Q000378:metabolism / Q000633:toxicity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; D034741:RNA, Small Interfering