Promises and Challenges in Developing RNAi as a Research Tool and Therapy for Neurodegenerative DiseasesXia X.G. · Zhou H. · Xu Z.
RNA interference (RNAi) is a recently discovered mechanism that is conserved in a wide range of eukaryotic species. Triggered by double-stranded RNA, RNAi identifies and destroys the mRNA that shares homology with the double-stranded RNA. Because of its specificity, RNAi has a high potential for being a powerful investigative and therapeutic tool. Indeed, its use as a reverse genetics tool to determine gene functions in invertebrates and cultured mammalian cells has already been experiencing an explosive growth. Gratifyingly we have also seen its application in dissecting neurodegeneration pathways in vitro. Although early studies suggested that RNAi could be readily adapted for in vivo studies in mammals using the transgenic technology, difficulties including low transgenicity and low RNAi efficacy have emerged, which has prevented the wide use of transgenic RNAi. The potential of RNAi therapy for human diseases has been a great source of excitement. Several new studies have demonstrated this concept in animal models of neurodegenerative disease. In this review, we highlight the recent literature and our own data in applying RNAi in research and therapy in the area of neurodegenerative diseases. We discuss the present and future challenges in the full realization of the potential for RNAi.
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