Gene silencing in rat-liver and limb grafts by rapid injection of small interference RNA.
Genetic modification is a promising therapeutic strategy for organ transplantation. In previous studies, we introduced a nonviral method of gene transfer to donor grafts using an organ-selective injection technique to up-regulate gene expression. Based on the attractive methodology of RNA interference for silencing a particular gene expression, we applied our catheter-based injection method to transfer small interference RNA (siRNA)-green fluorescence protein (GFP) into liver and limb grafts. We first quantified the interfering activity after the systemic delivery of siRNA in the liver of Alb-DsRed2 transgenic (Tg) rats using in vivo bioimaging system. Then, using GFP Tg Lewis rats as donors, transient down-regulation of the GFP expression was achieved both in liver- and limb-transplantation models by the preoperative rapid injection of siRNA. Genetic modification by siRNA may provide new therapeutic options for down-regulation of endogenous antigenicity.
Sato
Yuki
Y
Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0498, Japan.
Ajiki
Takashi
T
Inoue
Seiichiro
S
Fujishiro
Jun
J
Yoshino
Hiroyuki
H
Igarashi
Yuka
Y
Hakamata
Yoji
Y
Kaneko
Takashi
T
Murakami
Takashi
T
Kobayashi
Eiji
E
D000818:Animals; D030801:Animals, Genetically Modified; D020868:Gene Silencing; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D007267:Injections; D016031:Liver Transplantation / Q000502:physiology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D051381:Rats
D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins