Versatile Strategies of Nucleic Acid Synthesis for Rational Design and Biomedical Applications

Abstract

Nucleic acids, serving as both a repository for genetic information and the basis for biological activity, can be regarded as highly ordered functional molecules. Oligonucleotides (ONs) are oligomers of nucleic acids that can now be obtained by chemical synthesis. The ONs thus obtained have been approved as nucleic acid therapeutics for the treatment of various diseases. Importantly, chemically modified non-natural ONs with augmented functionality are useful when the functions of natural ONs fall short of achieving therapeutic efficacy. Chemical modification of ONs can also facilitate their complexation with other functional materials and further enhance the functionality of the resulting hybrid materials. Examples of such modifications include the combination of ONs with small molecular compounds, peptides, proteins, or highly ordered nanostructures with enhanced biological stability as building blocks for self-assembly. Thus, strategies for the precise chemical synthesis of ONs will play an important role in the sustained progress of biomedical materials.