Background: The discovery that short oligonucleotides, termed
aptamers, can fold into three dimensional structures that allow them to
selectively bind and inhibit the activity of pathogenic proteins is now over
25 years old. The invention of the SELEX methodology heralded in an era in
which such nucleic acid-based ligands could be generated against a wide
variety of therapeutic targets.
Results: A large number of aptamers have
now been identified by combinatorial chemistry methods in the laboratory and
moreover, an increasing number have been discovered in nature. The
affinities and activities of such aptamers have often been compared to that
of antibodies, yet only a few of these agents have made it into clinical
studies compared to a large and increasing number of therapeutic antibodies.
One therapeutic aptamer targeting VEGF has made it to market, while 3
others have advanced as far as phase III clinical trials.
Conclusion: In this manuscript, we hope the reader appreciates that the success of aptamers
becoming a class of drugs is less about nucleic acid biochemistry and more
about target validation and overall drug chemistry.