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Stealth Biotech Launched to Commercialize Technology Based on Targeting Specific microRNA:mRNA Interactions

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Stealth Biotech has announced its plans to target specific microRNA:mRNA interactions for development of oligonucleotide-based therapeutics. The company has filed fundamental patent applications covering methods and products used for blocking specific microRNA:mRNA interactions, a novel approach using antisense molecules that target microRNA binding sites on mRNAs.

MicroRNAs bind to target mRNAs to repress translation. About 500 human microRNAs has been discovered so far and it is estimated that at least on third of the human genes are subject to microRNA control. Thus, one microRNA typically regulates multiple mRNAs.

Recently, microRNAs have been demonstrated a role in various cancers, immunological conditions, metabolic disorders as well as viral infections, such as human immunodeficiency virus (HIV) infection, cytomegalovirus (CMV) infection and hepatitis C (HCV) infection.

Current approaches for interfering with microRNA pathways center on direct antisense inhibition of microRNAs. So far, this approach has demonstrated promise e.g. for treatment of hepatitis C infection and glioblastoma.

“With the discovery of RNA interference, the interest in oligonucleotide-based therapeutics has exploded”, said founder and CEO, Thorleif Moller, Ph.D. “The first wave was siRNAs and the second wave is microRNA based therapeutics, such as inhibitory antisense molecules targeting microRNAs.”

Continuing explaining the rationale of the company’s approach to targeting microRNA pathways, Thorleif Moller said, “Targeting microRNAs with antisense molecules will affect the activity of many downstream genes, since microRNAs are in general promiscuous and control the activity of many mRNAs. In some situations, this is bad news.”

“We want to use a much more subtle approach, which is to block single microRNA:mRNA interactions with so-called blockmirs. Blockmirs are antisense oligonucleotides that bind to a microRNA binding site on an mRNA and thereby prevent the microRNA from regulating only that specific mRNA, while still allowing the microRNA to control the rest of its target mRNAs,” Moller continued.

“And importantly, any off target binding of a blockmir is not expected to have any effect, because the blockmir functions via a steric block mechanism and consequently only activating oligonucleotides, where off target binding results in unintended mRNA degradation. It is estimated that at least one third of human genes are subject to microRNA regulation and it is also becoming increasingly clear that microRNAs play a role in many diseases.”