Liver-targeted hydrodynamic gene therapy: Recent advances in the technique.
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 inin vivogene-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 vivogene-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.
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.
Takeshi
T
Yokoo
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.
Kenya
K
Kamimura
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.
Hiroyuki
H
Abe
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.
Yuji
Y
Kobayashi
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.
Tsutomu
T
Kanefuji
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.
Kohei
K
Ogawa
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.
Ryo
R
Goto
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
M
Oda
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.
Takeshi
T
Suda
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.
Shuji
S
Terai
D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007267:Injections / Q000295:instrumentation; D008107:Liver Diseases / Q000628:therapy*; D023421:Models, Animal
Gene therapy; Hydrodynamic gene delivery; Image-guided; Liver; Non-viral