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Alnylam And Collaborators Publish Novel Method For Detection Of Tissue-Specific, RNAi-Mediated Gene Silencing

Stocks in this article: ALNY

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today the publication of a new paper describing a novel technique called circulating Extracellular RNA Detection (cERD). The paper, titled “ Tissue-specific gene silencing monitored in circulating RNA” (Sehgal et al., RNA, doi:10.1261/rna.042507.113) appears online as an Advance Article in the journal RNA. The cERD method enables the quantification of circulating messenger RNA (mRNA) and micro-RNA (miRNA) as a way of monitoring tissue-specific RNA silencing. It also enables confirmation of an RNAi-mediated mechanism of action using a PCR-based technique. The cERD method could have broad applicability in clinical studies since it allows for monitoring of tissue-specific mRNA levels using a non-invasive technique.

“Detection of target gene knockdown is typically made possible by measurement and quantification of mRNA levels in tissue samples and, if the target protein is secreted, corresponding protein levels in serum or plasma. Further, establishing proof of mechanism for RNAi therapeutics involves analysis of RNAi-mediated target mRNA cleavage with a PCR-based technique in tissue samples. However, the utility of these techniques is limited, since many proteins do not enter circulation, and the need to collect biopsies creates a significant challenge to the routine monitoring of mRNA expression levels or the RNAi mechanism of action in tissues,” said Rachel Meyers, Ph.D., Vice President of Research and RNAi Lead Development at Alnylam. “These new published data establish the applicability of the cERD method in multiple species, including rats and non-human primates, and thus the general utility of measuring circulating serum mRNA to confirm RNAi-mediated tissue gene silencing. Specifically, we have shown that changes in circulating RNA levels correspond closely to changes in tissue RNA levels, suggesting that RNA levels from biological fluids provide an accurate ‘real-time’ representation of tissue RNA status. These findings are important to the development of RNAi therapeutics, as the cERD method could be extended to the clinical setting to allow the routine, accurate, and frequent measurement of organ-specific target gene knockdown and/or RNAi mechanism without the need for tissue biopsies.”

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