Synthetic Nucleic Acid Capable of Post-Polymerization Functionalization and Evolution

Abstract

The functions of natural nucleic acids such as DNA and RNA have transcended from serving as the primary information carrier in cells and have emerged as a new class of functional material with applications encompassing medicine, diagnosis, and research tools. While the vulnerability of natural nucleic acids to nuclease degradation as well as the lack of chemical functionality have imposed a significant constraint on their ever-expanding applications, scientists have put in the effort to develop new classes of synthetic nucleic acids (XNAs) to overcome current limitations. In this dissertation, we will describe the development of a novel XNA oligonucleotide structure, the “click handle-modified FANA” (cmFANA), as the next-generation nucleic acid-based biopolymer that is capable of post-polymerization functionalization and evolution. In this dissertation, we divide our graduate research into three chapters: the development of the essential building block for cmFANA and the synthesis of cmFANA oligonucleotide as Chapter 1; the evolution and application of cmFANA as a sugar-presenting affinity reagent that targets disease-related Carbohydrate-Binding Proteins (CBPs) as Chapter 2; and other collaboration projects as Chapter 3. Together, we described a highly potential XNA structure that goes beyond established impressions of nucleic acids and carries the ability to be a versatile platform technology.