A new approach for therapeutic use by RNA interference in the brain.

RNA interference (RNAi) is a gene silencing phenomenon that is induced by ribonucleoprotein complexes containing 21-28 nucleotides (nt) of double-stranded RNA (si/miRNA). Although this phenomenon occurs in an inherent manner, it can also be induced in an artificially manipulated manner. Recently, the understanding of RNAi mechanisms has progressed from that in plants to that in mammals. As RNAi is a highly efficient and readily available procedure to knockdown specific targets, it can possibly be used as a new technique providing many researchers and clinicians with opportunities for its experimental use and prospective clinical application. Consequently, there has been a rush of elucidation of the effective sequences of siRNAs used for the knockdown of the targets in many fields, including neuroscience and experiments for neurological disorders. However, in many cases, it is difficult to effectively introduce si/miRNA into cells without causing injury to the recipient cells. Apart from the off-target effects and the pathogenic property of si/miRNA per se, which are designed and produced, the possibility and intensity of cell injury by RNAi depends on the method employed for the introduction of si/miRNA. Possible methods include si/miRNA delivery systems using liposome, polyethylenimine (PEI), electroporation, and viral infection. Currently, various methods for delivering si/miRNA into cells have been developed and challenged. Here, I review the advantages, disadvantages, and perspective of employing the RNAi procedure in the brain. Given that the disadvantages of RNAi can be overcome, the clinical application of RNAi technologies may be useful in realizing the elimination of pathogenic genes not only in the brain, but also in the other organs in the near future.