Therapeutics Advances
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2016; 22(40): 8862-8868
Published online Oct 28, 2016. doi: 10.3748/wjg.v22.i40.8862
Liver-targeted hydrodynamic gene therapy: Recent advances in the technique
Takeshi Yokoo, Kenya Kamimura, Hiroyuki Abe, Yuji Kobayashi, Tsutomu Kanefuji, Kohei Ogawa, Ryo Goto, Masafumi Oda, Takeshi Suda, Shuji Terai
Takeshi Yokoo, Kenya Kamimura, Hiroyuki Abe, Yuji Kobayashi, Tsutomu Kanefuji, Kohei Ogawa, Ryo Goto, Takeshi Suda, Shuji Terai, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata 951-8510, Japan
Masafumi Oda, Institute for Research Collaboration and Promotion, Niigata University, Niigata, Niigata 951-8510, Japan
Author contributions: Yokoo T, Kamimura K, Abe H, Kobayashi Y, Kanefuji T, Ogawa K, Goto R, Oda M, Suda T and Terai S all contributed to this paper.
Supported by in part Grant-in-Aid for Scientific Research from the Japanese Society for the Promotion of Sciences, No. 26860354 to Kamimura K, No. 16K19333 to Yokoo T, and No. 26293175 to Terai S.
Conflict-of-interest statement: The authors declare that they have no current financial arrangement or affiliation with any organization that may have a direct influence on their work.
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:
Correspondence to: Kenya Kamimura, MD, PhD, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachido-ri, Chuo-ku, Niigata 951-8510, Japan.
Telephone: +81-25-2272207 Fax: +81-25-2270776
Received: July 4, 2016
Peer-review started: July 6, 2016
First decision: July 29, 2016
Revised: August 3, 2016
Accepted: August 23, 2016
Article in press: August 23, 2016
Published online: October 28, 2016

One of the major research focuses in the field of gene therapy is the development of clinically applicable, safe, and effective gene-delivery methods. Since the first case of human gene therapy was performed in 1990, a number of gene-delivery methods have been developed, evaluated for efficacy and safety, and modified for human application. To date, viral-vector-mediated deliveries have shown effective therapeutic results. However, the risk of lethal immune response and carcinogenesis have been reported, and it is still controversial to be applied as a standard therapeutic option. On the other hand, delivery methods for nonviral vector systems have been developed, extensively studied, and utilized in in vivo gene-transfer studies. Compared to viral-vector mediated gene transfer, nonviral systems have less risk of biological reactions. However, the lower gene-transfer efficiency was a critical hurdle for applying them to human gene therapy. Among a number of nonviral vector systems, our studies focus on hydrodynamic gene delivery to utilize physical force to deliver naked DNA into the cells in the living animals. This method achieves a high gene-transfer level by DNA solution injections into the tail vein of rodents, especially in the liver. With the development of genome editing methods, in vivo gene-transfer therapy using this method is currently the focus in this research field. This review explains the method principle, efficiency, safety, and procedural modifications to achieve a high level of reproducibility in large-animal models.

Keywords: Gene therapy, Liver, Hydrodynamic gene delivery, Non-viral, Image-guided

Core tip: Among a number of nonviral vector systems, hydrodynamic gene delivery has been used to study human diseases. The major advantage of the method is the simple and easy step to deliver naked DNA into living animal cells by physical force. The original method modification of injecting the DNA solution into a rodent tail vein has made it applicable in large animals. This method of delivering naked DNA can contribute to treat, not only liver disease but also other systemic diseases that can be cured by facilitating/altering gene expression through the liver.