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Medicine

RNA as drug and antidote

Nature volume 419, pages 23–24 (2002)Cite this article

The biggest cause of serious illness and premature death in Western societies today is the blockage of blood vessels by abnormal blood clots1,2,3. On page 90 of this issue Rusconi and colleagues4 describe how they discovered a new drug that prevents blood clotting, and how they designed an antidote. The drug is an RNA 'aptamer', the sequence of which was found by iterative in vitro selection from a large combinatorial library of RNAs, screened for binding to a protein that promotes blood coagulation. Aptamers can be made of RNA or DNA, and they achieve their target-binding selectivity by virtue of the unique shapes they adopt through the formation of internal base pairs. Coagulation proteins are popular targets for both traditional and aptamer-based drugs, because they are available pure in soluble form, and their activity can be readily measured in assays of blood-clotting time or by their cleavage of small, colour-generating substrates5.

Normally, this process represents a vital first line of defence against blood loss. But a clot or platelet plug in the wrong place can cause a heart attack or stroke, by preventing blood flow and therefore oxygen supply to a particular area of tissue — hence the importance of drugs that inhibit blood clotting. Drugs that block the production of thrombin are termed anticoagulants, whereas those that inhibit platelet function are called antiplatelet agents. Remarkably, until quite recently there was only one class of antiplatelet agent, aspirin and its relatives, and only two classes of anticoagulant, heparins and antagonists of vitamin K, in widespread clinical use. Even more surprisingly, these were discovered (or introduced to the clinic) as long ago as 1900, 1916 and 1940, respectively. So the anti-clotting armamentarium remained sparsely stocked for most of the past century. Some innovative approaches have, however, started to fill it.

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Figure 1: How blood clots.

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  1. Faculty of Medicine, Imperial College of Science, Technology and Medicine, Haemostasis Research, MRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

    Edward Tuddenham

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Correspondence to Edward Tuddenham.

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Tuddenham, E. RNA as drug and antidote. Nature 419, 23–24 (2002). https://doi.org/10.1038/419023a

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