title: Artificial Control of Gene Silencing Activity Based on siRNA Conjugation with Polymeric Molecule Having Coil-Globule Transition Behavior.
abstract: A new strategy for controlling gene silencing activity of siRNA in the cell was developed in the present study. siRNA was linearly conjugated with PNIPAAm, where coil-globule transition of the conjugated PNIPAAm allows thermoresponsive exposure of the vicinal siRNA molecule; a coil form of PNIPAAm (T < LCST) inhibits siRNA interaction with gene silencing-related proteins due to the steric hindrance effect, while a globule form of PNIPAAm (T > LCST) allows a ready access of siRNA to gene silencing pathway. As a result, at T > LCST, PNIPAAm-siRNA elicited effective association of siRNA with a gene silencing-related protein of Ago2, while siRNA recruitment into the gene silencing pathway was significantly suppressed at T < LCST. Ultimately, gene silencing efficacy of PNIPAAm-siRNA was close to unconjugated siRNA at T > LCST (∼80%), while it was dramatically decreased to ∼20% at T < LCST, suggesting that coil-globule transition of the conjugated polymer can control the bioactivity of the vicinal siRNA molecule.
authors: Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology , R1-11, 4259, Nagatsuta, Midori-Ku, Yokohama, Kanagawa 226-8503, Japan.
authors: Noor Faizah
authors: NF
authors: Che Harun
authors: Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology , R1-11, 4259, Nagatsuta, Midori-Ku, Yokohama, Kanagawa 226-8503, Japan.
authors: Hiroyasu
authors: H
authors: Takemoto
authors: Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology , R1-11, 4259, Nagatsuta, Midori-Ku, Yokohama, Kanagawa 226-8503, Japan.
authors: Takahiro
authors: T
authors: Nomoto
authors: Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology , R1-11, 4259, Nagatsuta, Midori-Ku, Yokohama, Kanagawa 226-8503, Japan.
authors: Keishiro
authors: K
authors: Tomoda
authors: Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology , R1-11, 4259, Nagatsuta, Midori-Ku, Yokohama, Kanagawa 226-8503, Japan.
authors: Makoto
authors: M
authors: Matsui
authors: Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology , R1-11, 4259, Nagatsuta, Midori-Ku, Yokohama, Kanagawa 226-8503, Japan.
authors: Nobuhiro
authors: N
authors: Nishiyama
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D001483:Base Sequence; D004337:Drug Carriers / Q000737:chemistry*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008968:Molecular Conformation; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics*; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D034741:RNA, Small Interfering; C052970:poly-N-isopropylacrylamide