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Using RNA Interference to Downregulate G Protein-Coupled Receptors

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Technologies developed to interfere with gene transcripts were developed back in the 1980. However, it was not before the last decade that light was shed on the underlying mechanisms of what is now known as RNA interference. From then, RNAi was propelled to the forefront as a revolutionizing approach for basic research and clinical therapy. In the present chapter, we will present an overview of RNAi and its mechanisms with a focus on GPCRs applied to neuroscience. We will briefly detail the steps to move from the in vitro assessment to the in vivo proof-of-principle to further ensure appropriate clinical transfer. Examples of successful experiments will be given in each section. Advances, drawbacks, and future directions will be discussed with RNAi as an exciting new technology that can be used to treat GPCR-related neuropathologies intractable with commonly-used pharmacological agents.
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