SANTA CRUZ, Calif., July 24, 2012 /PRNewswire/ -- SomaGenics, Inc., a biotechnology company specializing in RNA-based technologies, announced the publication of a study reporting the mechanism of action of its sshRNAs, the class of molecules that forms the basis of the company's therapeutic platform. sshRNAs are small synthetic stem-loop (or hairpin) RNAs that the company's researchers have shown to be highly potent in knocking down target RNAs through an RNA interference (RNAi) mechanism. In the new study, the SomaGenics authors and their collaborators show that the two structurally distinct types of sshRNA, right-loop or R-type and left-loop or L-type, have different mechanisms of action, and each is different from the mechanisms of action of standard siRNAs and shRNAs.
The new study shows that sshRNAs do not require the enzyme Dicer for activity in cells, unlike standard larger hairpin RNAs and most microRNAs. Other results show that R- and L-type sshRNAs require different structural features to be highly active, and provide an explanation for how these features promote the gene silencing potency of each class of molecules. R-sshRNAs require that their loops be cleavable by a non-Dicer cellular enzyme for maximal activity, whereas L-sshRNAs function very well with their loops intact. In both types of hairpins, the non-active, "passenger" sequence is "sliced" by the key enzyme Argonaute-2, but in the case of L-sshRNAs, only the single small fragment of slicing is lost from the RNA-induced silencing complex (RISC) prior to engaging the target to be silenced, while for R-sshRNAs and siRNAs, two small fragments of slicing are removed. Interestingly, L-sshRNAs have a natural equivalent, the recently discovered microRNA miR-451, which also does not require Dicer activity to be incorporated into the RNAi machinery.
The new study appears online this week in Nucleic Acids Research. The lead author is Dr. Anne Dallas of SomaGenics, and coauthors include researchers from the University of California, San Francisco and Integrated DNA Technologies of Coralville, Iowa.
SomaGenics presents findings at recent liver meetings
SomaGenics' President and CEO, Dr. Brian Johnston, has given oral presentations on SomaGenics' therapeutic program against the hepatitis C virus (HCV) in two recent major international forums: the annual meeting of the European Association for the Study of Liver (EASL) in Barcelona, Spain (April 18-22), and the 14th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD) in Shanghai, China (June 21-25). In addition to the findings of the Nucleic Acids Research paper, Dr. Johnston described the success of SomaGenics and its collaborators from Roche and Tekmira Pharmaceuticals in using sshRNAs directed against HCV and formulated with lipid nanoparticles to achieve a large, sustained reduction in viral load in HCV-infected mice whose livers are largely populated with human hepatocytes (see SomaGenics press release, Sept. 20, 2011). With these results, SomaGenics' HCV program has successfully completed preclinical efficacy evaluation and is ready for clinical development.
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|SOURCE SomaGenics, Inc.|
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