Channelrhodopsins—Their potential in gene therapy for neurological disorders

Recently, channelrhodopsins (ChRs) have begun to be used to manipulate the neuronal activity, since they can be targeted to specific neurons or neural circuits using genetic methods. To advance the potential applications in the investigation and treatment of neurological disorders, the following types of basic research should receive extensive financial support. The spectral and kinetic properties of ChRs should be optimized according to the application by generating variants of ChRs or exploring new rhodopsins from other species. These ChRs should be targeted to the specific types of neurons involved in the neurological disorders through a gene expression system using cell- or tissue-specific promoters/enhancers as well as gene delivery systems with modified virus vectors. The methods have to be developed to apply the genes of interest with safety and long-term effectiveness. Sophisticated opto-electrical devices should be developed. Appropriate primate animal model systems should be established to minimize the structural differences between small animals such as rodents and human beings. In this paper, we will review the current progress in the basic research concerned with the potential clinical application of ChRs and discuss the future directions of research on ChRs so that they could be applied for human welfare.

► We discussed the way to apply ChRs for the treatment for neurological disorders. ► Variety of ChRs should be searched and optimized with molecular modification. ► Targeting methods should be investigated for the ChR expression with safety and effectiveness. ► Sophisticated opto-electrical devices should be developed. ► The appropriate primate animal model systems should be established.