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Alnylam, Mount Sinai Researchers Report Discovery of Small RNA Class in Flu


Researchers from Alnylam Pharmaceuticals and Mount Sinai School of Medicine reported this week the discovery of a new class of virus-produced small non-coding RNAs, dubbed small viral RNAs, that appear to play an important role in the replication of the influenza A virus.

"The discovery of svRNAs that play a critical role in flu virus replication opens the door for the development of novel RNA therapeutics for the treatment of flu infection, an area of major unmet need," Antonin de Fougerolles, Alnylam's vice president of research, immunology, metabolic, and viral diseases, said in a statement.

According to Alnylam, the research, which was published this week in the Proceedings of the National Academy of Sciences, "describes the discovery of influenza A svRNAs and their role as part of a viral mechanism to control the switch between transcription and replication, representing a new paradigm in virus biology."

The so-called svRNAs were found to "mediate their activity by direct association with the viral RNA polymerase enzyme, representing a distinct mechanism of action as compared with other classes on small non-coding RNAs, such as microRNAs, which act by controlling gene expression through interactions with target mRNAs," the company added.

Specific findings in the paper included that influenza A infection results in the expression of svRNAs that range from 22 to 27 nucleotides in length and correspond to the 5' end of each viral genomic RNA segment; expression of svRNA was found to correlate with the accumulation of vRNA and was found to be essential in converting RNA-dependent RNA polymerase activity from transcription toward genome replication; and that svRNA was detectable during the shift from viral transcription to replication in a broad range of influenza A virus subtypes across multiple host species, Alnylam said.

Further, inhibition of specific svRNAs using chemically modified, single-stranded anti-svRNA oligos triggered suppression of vRNA synthesis in a segment-specific manner and potently blocked viral infectivity, the company added.

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