An On/Off Switch for Drug Design

In theory, aptamers can specifically bind and modulate the activity of any protein for which they're designed.

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© 2004 Nature Publishing Group

The aptamer binds to activated factor IX preventing proteolytic cleavage of factor X. In the presence of antidote, the aptamer is released from factor IXa. The aptamer is stabilized by a 3'-3'-linked deoxythymidine at the 3'-end and by 2'fluoro-2'deoxy modifications at every pyrimidine residue. It carries a cholesterol modification at the 5' end to increase plasma residence time. (From M. Famulok, Nat Biotechnol, 22:1373–4, 2004.)

In theory, aptamers can specifically bind and modulate the activity of any protein for which they're designed. Aptamers fold into three-dimensional structures, based on their oligonucleotide sequences, and like antibodies specifically target proteins, distinguishing them from antisense or RNA interference (RNAi). Currently, at least 23 aptamer-based therapeutic agents are under clinical development.1

"There is a huge potential in aptamers," says Bruce Sullenger of Duke University Medical Center. But like other oligonucleotide-based therapies, they do not cross cell boundaries very well, ...

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