title: Cell-penetrating cationic siRNA and lipophilic derivatives efficient at nanomolar concentrations in the presence of serum and albumin.
abstract: Despite its considerable interest in human therapy, in vivo siRNA delivery is still suffering from hurdles of vectorization. We have shown recently efficient gene silencing by non-vectorized cationic siRNA. Here, we describe the synthesis and in vitro evaluation of new amphiphilic cationic siRNA. C₁₂-, (C₁₂)₂- and cholesteryl-spermine(x)-siRNA were capable of luciferase knockdown at nanomolar concentrations without vectorization (i.e. one to two orders of magnitude more potent than commercially available cholesteryl siRNA). Moreover, incubation in the presence of serum did not impair their efficiency. Finally, amphiphilic cationic siRNA was pre-loaded on albumin. In A549Luc cells in the presence of serum, these siRNA conjugates were highly effective and had low toxicity.
authors: Laboratoire de Chimie Génétique, C.A.M.B. UMR 7199, Université de Strasbourg and C.N.R.S., Laboratory of Excellence MEDALIS, Faculté de Pharmacie, F-67401 Illkirch, France.
authors: Phanélie
authors: P
authors: Perche
authors: Marc
authors: M
authors: Nothisen
authors: Jérémy
authors: J
authors: Bagilet
authors: Jean-Paul
authors: JP
authors: Behr
authors: Mitsuharu
authors: M
authors: Kotera
authors: Jean-Serge
authors: JS
authors: Remy
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D008055:Lipids / Q000737:chemistry; D049409:Luciferases, Firefly / Q000235:genetics; D009841:Oligonucleotides / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D044967:Serum; D013096:Spermine / Q000737:chemistry
chemical_list: D000418:Albumins; D008055:Lipids; D009841:Oligonucleotides; D034741:RNA, Small Interfering; D013096:Spermine; D049409:Luciferases, Firefly