RNAi Applications

RNAi is a straightforward method for inducing sequence-specific silencing of one or more genes of interest with the introduction of siRNAs. It has been a powerful tool to investigate gene function. Studies using RNAi have been performed in neuronal cells to examine the functional roles of individual genes in developing growth cones and neurite outgrowth (Eriksson et al. 2007; Hengst et al. 2006; J. Liu et al. 2007; Schmitz et al. 2007; Yanaka et al. 2007), ion channels (Geng et al. 2004; Lauver et al. 2006; Tahiliani et al. 2007), apoptosis (Yano et al. 2007; Zhang et al. 2007), and a variety of signaling pathways (Meuer et al. 2007; Sanada and Tsai 2005; G. X. Shi et al. 2006; Yamada et al. 2005). Furthermore, RNAi is now being used for the knockdown of gene expression in animals. It appears to apply in virtually all mammalian species, as exemplified by its capability for silencing genes in mice, rats, and goats (Peng et al. 2006; Zhou et al. 2007). Inducible RNAi based on the Cre-loxP system has also been developed in transgenic mice, enabling the investigator to control gene silencing spatially and temporally (Chang et al. 2004; Coumoul et al. 2005; Xia et al. 2006). Thus, it is possible to rapidly establish human genetic diseases as a whole-animal model without the difficulty and expense of embryonic stem cell and gene targeting.

RNAi can knock down specific genes, making it evident that RNAi may be used to disrupt the expression of disease-associated genes for therapeutic purposes. Recent findings have highlighted the possibility of RNAi as a potential therapeutic approach to many human diseases, although a number of challenges need to be addressed, such as the safety concerns and effective delivery of RNAi therapy. RNAi-based therapies for age-related macular degeneration (AMD) and respiratory syncytial virus (RSV) have already reached clinical trials. Moreover, therapies based on RNAi are also in preclinical development for other viral diseases (Rossi 2006), neurodegenerative disorders (Raoul et al. 2006; Xia et al. 2005), and cancers (Pai et al. 2006).

RNAi has become a frequently used tool in a wide range of biomedical research. It has provided a convenient method to study gene function via application of RNAi to cell lines, cultures, and embryonic stem cells. It is anticipated that new uses for this tool will continue to proliferate.

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