Progress in Chemically Modified Nucleic Acid Aptamers

Abstract

Nucleic acid aptamers are DNA/RNA-based ligands that specifically bind to their targets. Unlike antibodies, they can be created using in vitro selection systems and produced on a large-scale level at low cost using solid-phase oligonucleotide syntheses. After the methodology of systematic evolution of ligands by exponential enrichment (SELEX) for DNA/RNA aptamer selection was established in the early 1990s, their applications for diagnostic and therapeutic drugs as well as research reagents and biosensors have attracted considerable attention. In 2004, the first aptamer medicine, MACUGEN® (pegaptanib sodium injection), a chemically modified RNA aptamer, was approved by United States Food and Drug Administration (U.S. FDA). However, further improvements in biostability and functional expandability are needed in order to achieve modified nucleic acid aptamers with high binding affinities and specificities for a broad range of targets. Hence base-modified aptamers like SOMAmer™ and sugar-modified aptamers like xeno-nucleic acid (XNA) aptamers have currently come into the spotlight. Furthermore, the remarkable advances that have been made in recent years in sequencing technologies should significantly contribute to the development of nucleic acid aptamers as molecular tags for omics research and for use as clinical biomarkers. This chapter focuses on the initial attempts, recent advances, and future prospects for modified nucleic acid aptamer development and the related technologies.