Functional XNA and Biomedical Application

Functional nucleic acids can be generated in the laboratory by in vitro selection, which produces functional DNA and RNA molecules with user-defined properties such as ligand-binding affinity (i.e., aptamer) and reaction-accelerating capability (e.g., ribozyme). However, natural nucleic acids are inherently susceptible to nuclease-mediated degradation and contain relatively limited chemical functionalities. Xeno-nucleic acids (XNAs) are synthetic genetic polymers that are structurally distinct from natural DNA and RNA, and thus exhibit superior biological stability and chemical diversity. Applying the in vitro selection technology to XNA has been a daunting challenge because it demands expertise in both nucleic acid chemistry and protein engineering. Recent advances in these areas have enabled a number of successful in vitro selection experiments to identify functional XNA molecules. In this chapter, some basics on functional nucleic acid and in vitro selection will be first introduced, followed by descriptions of various XNA chemistries that will be covered in this chapter. This chapter will then be focused mostly on two specific types of XNAs: threose nucleic acid (TNA) and 2’-deoxy-2’-fluoroarabinose nucleic acid (FANA), because several TNA and FANA aptamers and enzymes have been reported. For each type of XNA, development of polymerases capable of recognizing XNA substrates will be summarized. Examples of XNA aptamers and enzymes will then be covered, including their identification, characterization, and potential application in cancer and viral theranostics. Aptamers and enzymes based on a few other XNA chemistries will also be reviewed. Lastly, thoughts on future directions will be provided.