Liver-targeted hydrodynamic gene therapy: Recent advances in the technique

• Published in: World journal of gastroenterology : WJG Vol. 22; no. 40; pp. 8862 - 8868
• Main Authors: Yokoo, Takeshi, Kamimura, Kenya, Abe, Hiroyuki, Kobayashi, Yuji, Kanefuji, Tsutomu, Ogawa, Kohei, Goto, Ryo, Oda, Masafumi, Suda, Takeshi, Terai, Shuji
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 28.10.2016
• Subjects: Animals; Genetic Therapy - methods; Humans; Injections - instrumentation; Liver Diseases - therapy; Models, Animal; Therapeutics Advances; Hydrodynamic gene delivery; Image-guided; Gene therapy; Liver; Non-viral
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v22.i40.8862

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-vectormediated 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.