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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2015; 21(13): 3813-3825
Published online Apr 7, 2015. doi: 10.3748/wjg.v21.i13.3813
New gene therapy strategies for hepatic fibrosis
Adriana M Salazar-Montes, Luis D Hernández-Ortega, Martha S Lucano-Landeros, Juan Armendariz-Borunda
Adriana M Salazar-Montes, Luis D Hernández-Ortega, Martha S Lucano-Landeros, Juan Armendariz-Borunda, Department of Molecular Biology and Genomics, Institute for Molecular Biology and Gene Therapy, University of Guadalajara, Guadalajara, Jalisco 44281, México
Author contributions: Salazar-Montes AM is the first author and wrote the article; Hernández-Ortega LD and Lucano-Landeros MS performed the literature search and created the figure; Armendariz-Borunda J was the principal investigator who contributed to the article writing, revision and supervision.
Conflict-of-interest: Authors have no conflicts of interest to disclose for this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Juan Armendáriz-Borunda, Department of Molecular Biology and Genomics, Institute for Molecular Biology and Gene Therapy, University of Guadalajara, Sierra Mojada 950, Guadalajara, Jalisco 44281, México. armdbo@gmail.com
Telephone: +52 -33-10585317 Fax: +52-33-10585318
Received: October 15, 2014
Peer-review started: October 15, 2014
First decision: November 14, 2014
Revised: December 11, 2014
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: April 7, 2015
Abstract

The liver is the largest internal organ of the body, which may suffer acute or chronic injury induced by many factors, leading to cirrhosis and hepatocarcinoma. Cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of the normal hepatic structure, regenerative nodules and fibrotic tissue. Cirrhosis is associated with a high co-morbidity and mortality without effective treatment, and much research has been aimed at developing new therapeutic strategies to guarantee recovery. Liver-based gene therapy has been used to downregulate specific genes, to block the expression of deleterious genes, to delivery therapeutic genes, to prevent allograft rejection and to augment liver regeneration. Viral and non-viral vectors have been used, with viral vectors proving to be more efficient. This review provides an overview of the main strategies used in liver-gene therapy represented by non-viral vectors, viral vectors, novel administration methods like hydrodynamic injection, hybrids of two viral vectors and blocking molecules, with the hope of translating findings from the laboratory to the patient´s bed-side.

Keywords: Gene therapy, Hepatic fibrosis, Viral vectors, Non-viral vectors

Core tip: Cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration. Cirrhosis is a disease without effective treatment and new therapeutic strategies to accomplish healing are continuously being sought. Liver-based gene therapy has been used to improve liver function using viral and non-viral vectors. This review provides an overview of the main strategies used in liver-gene therapy, with the hope of finding a niche application in a given clinical scenario.