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Stealth Biotech launched to commercialize technology based on targeting specific microRNA:mRNA interactions.
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Stealth Biotech launched to commercialize technology based on targeting specific microRNA:mRNA interactions.

Stealth Biotech launched to commercialize technology based on targeting specific microRNA:mRNA interactions.
News

Stealth Biotech launched to commercialize technology based on targeting specific microRNA:mRNA interactions.

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Stealth Biotech announced today its plans to target specific microRNA:mRNA interactions for development of novel 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 Møller, 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 Møller 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. 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 has an effect if it binds to its intended target site. This is different from e.g. siRNAs and RNase H 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. Already many situations have been identified, in which we believe that disrupting single microRNA:mRNA interactions has potential therapeutic application and we have only seen a fraction of the opportunities that science will provide in the coming years, while unraveling microRNA regulatory pathways and their contribution to disease.

One potential use of blockmirs is for treatment of Hepatitis C infection. It is known that microRNA-122 facilitate replication of hepatitis C virus and therefore it has been suggested to target microRNA-122 with an inhibitory antisense molecule for the treatment of hepatitis c infection. However, microRNA-122 is very abundant in liver cells and we suspect that blocking its function might have adverse effects, because of deregulation of cellular mRNAs under microRNA-122 control. Therefore, we want to use a blockmir to specifically block the interaction between microRNA-122 and its target site in the 5’ untranslated region of the HCV viral genome, while not affecting the normal role of microRNA-122 in liver cells.”

Commenting on the near future of the company Thorleif Møller said, “Focus during the last year has been on securing IP for our blockmir approach and we have filed patent applications covering blockmirs per se, methods of blocking specific microRNA:mRNA interactions and also methods of microRNA target identification and validation. Now, we want to take the next step, which is to consolidate our IP-portfolio further and to identify clinical candidates. To this end, we are currently entering into research collaborations with academia and also discussing partnerships with industry players in the fields of oligonucleotides and delivery. Needless to say, we are currently also working with securing funding for commercialisation of the technology.”

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