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European Biopharmaceutical Review

Oligonucleotide Drugs – Within Sight of the Finish Line?

Henrik Ørum at Santaris Pharma reviews new developments in the field of antisense therapies and considers how close we are to a breakthrough

The past decade has witnessed a tremendous increase in our knowledge of the human genome and the link between genes and disease. Soon, sequence and functional information will be available on all the human genes, of which thousands are expected to be attractive points for pharmaceutical intervention. Harvesting the medical potential of this vast number of novel targets holds great promise for better and safer treatments of more diseases. At the same time, however, it also presents a formidable challenge to the drug industry.

Part of the challenge is financial and relates to the excessive costs associated with the discovery and development of drugs against novel targets by contemporary approaches, such as small molecules and antibodies. Part of the challenge, however, is also technical and relates to the fact that many of the new gene targets encode intracellular proteins that act through protein-protein interactions – a class of proteins that have proven difficult, and often impossible – to target. Add to that challenge, the emergence of a novel, abundant class of noncoding, regulatory RNAs (microRNAs) that seems poised to become therapeutically-relevant targets and which will almost certainly be non-drugable by traditional approaches.

The concept of using short synthetic oligonucleotides as drugs (antisense therapy) provides the means to meet these challenges. Notably, antisense therapy is applicable to all targets and offers a number of advantages that can both shorten drug development time and reduce the risk of costly failures. These include the ability to rationally design the drugs for maximum target affinity and specificity; ease of synthesis and rapid selection/profiling of lead compounds in vitro and in vivo; predictability of ADME and toxicity profiles; and use of well established, uniform and cost-competitive processes for large-scale manufacture.


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Henrik Ørum is co-founder of Cureon A/S, now merged with Pantheco A/S to create Santaris Pharma A/S, where he acts as CSO and VP of Business Development. He was previously Director R&D and CSO at PNA Diagnostics A/S (formerly a subsidiary of Boehringer Mannheim and Hoffmann-La Roche). Henrik is also co-founder and a previous board member of Exiqon A/S – a diagnostics company that was floated on the Copenhagen Stock exchange in May 2007. He holds a MSc in Molecular Biology from the Technical University of Copenhagen, a PhD in Molecular Biology from the Medical University of Copenhagen and undertook post-doctoral studies at the Copenhagen Royal School of Pharmacy. He is the author and co-author of more than 40 scientific publications and books and holds several patents. He is often invited to speak at scientific and biotech conferences and symposiums.
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