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World J Gastroenterol. Oct 28, 2014; 20(40): 14696-14705
Published online Oct 28, 2014. doi: 10.3748/wjg.v20.i40.14696
Small RNA- and DNA-based gene therapy for the treatment of liver cirrhosis, where we are?
Kyung-Hyun Kim, Kwan-Kyu Park
Kyung-Hyun Kim, Kwan-Kyu Park, Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 705-718, South Korea
Author contributions: All authors contributed equally to this paper.
Supported by National Research Foundation of Korea Grant funded by the Korean Government, No. 2012R1A1A401015639
Correspondence to: Kwan-Kyu Park, MD, PhD, Department of Pathology, College of Medicine, Catholic University of Daegu, 3056-6 Daemyung 4-Dong, Nam-Gu, Daegu 705-718, South Korea. kkpark@cu.ac.kr
Telephone: +82-53-6504149 Fax: +82-53-6504834
Received: October 23, 2013
Revised: April 3, 2014
Accepted: June 2, 2014
Published online: October 28, 2014
Processing time: 371 Days and 6.1 Hours
Abstract

Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure. Based on the underlying cellular and molecular mechanisms of a liver fibrosis, there has been proposed several kinds of approaches for the treatment of liver fibrosis. Recently, liver gene therapy has been developed as an alternative way to liver transplantation, which is the only effective therapy for chronic liver diseases. The activation of hepatic stellate cells, a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis. Several targeted strategies have been developed, such as antisense oligodeoxynucleotides, RNA interference and decoy oligodeoxynucleotides to overcome this barriers. With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis, and particularly, of the targeted gene therapy using short RNA and DNA segments.

Keywords: Liver cirrhosis; Gene therapy; Oligodeoxynucleotides; Antisense; Small interfering RNA; Micro RNA; Decoy

Core tip: Recent advances in understanding the mechanisms underlying liver fibrogenesis, including regulation of inflammatory cytokine signaling, the dynamic process of hepatic stellate cell activation and extracellular matrix degradation. The only option for patients suffering from severe and late-stage cirrhosis is liver transplantation; however, it is limited by the number of available donor organs. Therefore, development of new therapeutic strategies for liver fibrosis and cirrhosis are needed. This review focuses on the recent advances relating to the therapeutic application of liver fibrogenesis through the modulation of gene expression.