ABSTRACT
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28.1 INTRODUCTION
Aptamers can be considered as the oligonucleotide analogs of antibodies, functioning to bind specific molecular targets with high affinity and high specificity. Since the invention of the SELEX process used to generate aptamers over 15 years ago, significant advances have been made in both our understanding of how aptamers fold and function and in our ability to generate aptamers with
properties suitable for practical therapeutic applications. As with the development of monoclonal antibody therapeutics, a number of challenges have been addressed in the move from the lab into the clinic, including dramatic improvements in the pharmacokinetic properties of aptamers, the ability to cost-effectively synthesize large quantities of clinical-grade aptamers, and the ability to tune the specificity and affinity of aptamers for appropriate therapeutic targets. This chapter reviews the process by which these molecules are discovered and summarizes the properties of those that have been developed for therapeutic applications. A handful of example therapeutic programs are described, focusing in particular upon Macugen (pegaptanib), the first aptamer to be approved and marketed for therapeutic use. Remaining challenges in broadening the scope of aptamer therapeutic applications are presented, together with initial efforts at addressing the limitations of the current generation of molecules.
