Development of Cell-Penetrating Asymmetric Interfering RNA Targeting Connective Tissue Growth Factor
Jihye Hwang, Chanil Chang, Ji Hyun Kim, Chang Taek Oh, Ha Neul Lee, Changki Lee, Donghoon Oh, Changjin Lee, Beomjoon Kim, Sun Woo Hong, Dong-Ki Lee, Jihye Hwang, Chanil Chang, Ji Hyun Kim, Chang Taek Oh, Ha Neul Lee, Changki Lee, Donghoon Oh, Changjin Lee, Beomjoon Kim, Sun Woo Hong, Dong-Ki Lee
Abstract
Connective tissue growth factor (CTGF) is a multifunctional matricellular protein, playing a role as a central mediator in tissue remodeling and fibrosis. A number of reports have shown the pivotal roles of CTGF in the progression of fibrosis, suggesting CTGF as a promising therapeutic target for the treatment of fibrotic disorders including hypertrophic scars and keloids. In this study, we present the development of an interfering RNA molecule that efficiently inhibits the expression of CTGF via RNA interference mechanism both in vitro and in vivo. Chemical modifications were introduced to the asymmetric interfering RNA (asiRNA) backbone structure. The resulting RNA molecule, termed cell-penetrating asiRNA (cp-asiRNA), entered into cells and triggered RNA interference-mediated gene silencing without delivery vehicles. The gene-silencing activity of cp-asiRNA targeting CTGF (cp-asiCTGF) was examined both in vitro and in vivo. Furthermore, the administration of cp-asiCTGF in the rat skin excision wound model efficiently reduced the induction of CTGF and collagens during the wound-healing process. These results suggest that the cp-asiCTGF molecule could be developed into antifibrotic therapeutics such as antiscar drugs.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed