Published online Oct 28, 2016. doi: 10.3748/wjg.v22.i40.8862
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
Processing time: 113 Days and 22 Hours
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.
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.