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MicroRNA – a technology to rival RNAi?

One of the hot topics in drug discovery at the moment is microRNA (miRNA). MicroRNAs are short pieces of single-stranded RNA, about 21-23 bases long, that bind to matching sequences of messenger RNA, thereby rendering them double-stranded and inhibiting the production of the corresponding protein.

MicroRNAs are involved in the regulation of gene expression in both plants and animals. In humans, they appear to be involved in many biological processes in both health and disease, and as such are attractive potential drug targets. A novel class of chemically engineered oligonucleotides known as antagomirs has emerged as specific antagonists of miRNA.

Some of the latest research on antagomirs as drug candidates emerged recently at the Fifth Annual European Vascular Genomics Network Meeting at Bad Hofgastein in Austria. Researchers from the University of Frankfurt in Germany reported that they have identified a family of miRNAs that seem to be involved in angiogenesis and that are highly expressed in cells from patients with cardiac ischaemia or coronary artery disease.

Other experiments indicated that these miRNAs inhibit the repopulation of ischaemic tissues by endothelial cells. The German researchers therefore developed an antagomir that inhibited the miRNAs and found in preliminary experiments that it promoted recovery of cardiac function in animal models of ischaemia.

MicroRNAs are also being investigated as drug targets in other conditions, such as cancer and autoimmune/inflammatory diseases, and a number of companies have been set up specifically to exploit this area of research. For example, Isis and Alnylam have set up joint venture, Regulus Therapeutics, which is looking at a number of therapeutic areas, and earlier this year Asuragen transferred its miRNA intellectual property to a new company, Mirna Therapeutics, which focuses on cancer applications.

A third company, Miragen Therapeutics, is developing an antagomir for the treatment of heart failure, while in May of this year, the Danish company Santaris Pharma began a Phase I study of its miRNA antagonist, SPC-3649, which is targeted at hepatitis C.

MicroRNA has been likened to RNA interference (RNAi) as a therapeutic approach. RNAi is showing some promise, with at least one product (Opko Health’s bevasiranib sodium, for the treatment of wet age-related macular degeneration) in Phase III trials. With agents that antagonise miRNA just starting to enter the clinic, look out for a contest to see which approach is more effective and which (if either) is first to market.

Posted 01/12/2008 15:43:18 PM
by Dr Peter Charlish,
Analyst

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