Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 28, 2015; 7(6): 859-873
Published online Apr 28, 2015. doi: 10.4254/wjh.v7.i6.859
Progress and prospects of engineered sequence-specific DNA modulating technologies for the management of liver diseases
Samantha A Nicholson, Buhle Moyo, Patrick B Arbuthnot
Samantha A Nicholson, Buhle Moyo, Patrick B Arbuthnot, Wits/SA MRC Antiviral Gene Therapy Research Unit, School of Pathology, Health Sciences Faculty, University of the Witwatersrand, Wits 2050, Johannesburg, South Africa
Author contributions: Nicholson SA, Moyo B and Arbuthnot PB contributed to this paper.
Supported by The South African National Research Foundation (NRF, GUNs 81768, 81692, 68339, 85981 and 77954); Poliomyelitis Research Foundation; Claude Leon Foundation (SAN); The University of the Witwatersrand Research Council (BM) and Medical Research Council.
Conflict-of-interest: The authors declare no conflict of interest.
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: Patrick B Arbuthnot, Wits/SA MRC Antiviral Gene Therapy Research Unit, School of Pathology, Health Sciences Faculty, University of the Witwatersrand, 7 York Road, Parktown, Private Bag 3, Wits 2050, Johannesburg, South Africa. patrick.arbuthnot@wits.ac.za
Telephone: +27-11-7172365 Fax: +27-11-7172395
Received: September 11, 2014
Peer-review started: September 13, 2014
First decision: September 28, 2014
Revised: December 16, 2014
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: April 28, 2015
Processing time: 232 Days and 3.2 Hours
Abstract

Liver diseases are one of the leading causes of mortality in the world. The hepatic illnesses, which include inherited metabolic disorders, hemophilias and viral hepatitides, are complex and currently difficult to treat. The maturation of gene therapy has heralded new avenues for developing effective intervention for these diseases. DNA modification using gene therapy is now possible and available technology may be exploited to achieve long term therapeutic benefit. The ability to edit DNA sequences specifically is of paramount importance to advance gene therapy for application to liver diseases. Recent development of technologies that allow for this has resulted in rapid advancement of gene therapy to treat several chronic illnesses. Improvements in application of derivatives of zinc finger proteins (ZFPs), transcription activator-like effectors (TALEs), homing endonucleases (HEs) and clustered regularly interspaced palindromic repeats (CRISPR) and CRISPR associated (Cas) systems have been particularly important. These sequence-specific technologies may be used to modify genes permanently and also to alter gene transcription for therapeutic purposes. This review describes progress in development of ZFPs, TALEs, HEs and CRISPR/Cas for application to treating liver diseases.

Keywords: Gene therapy; Zinc fingers; Transcription activator-like effectors; Clustered regularly interspaced short palindromic repeats; Homing endonucleases; Liver diseases

Core tip: The treatment of liver diseases is varied and often complicated. Gene editing is being developed to treat a variety of chronic disorders and has exciting potential for curing hepatic diseases. Engineering of derivatives of zinc finger proteins, transcription activator-like effectors, homing endonucleases and clustered regularly interspaced palindromic repeats potentially enables sequence-specific gene editing. These DNA binding proteins may be used to alter genes permanently or to influence the epigenetic status of liver cells for therapeutic benefit.