Constructing Artificial Nucleobase Compilation to Enable Precise Molecular Medicine

Nucleic acids are the hereditary information storage medium of life. Due to its high programmability and good biocompatibility, the applications of nucleic acids are not limited to their natural function. However, the efficiency of nucleic acids is often hampered by inherent limitations in numerous practical applications, including limited access to complex functional patterns due to only four building blocks, facile degradation by nucleases, rapid renal clearance, poor pharmacokinetic properties, and so on. To end this, the researchers developed unnatural base pairs (UBPs) and numerous artificial analogues of nucleosides and oligonucleotides in recent decades. The developed UBPs and nucleoside base analogues together constitute artificial nucleobase compilation, which promotes the development of biomedical sciences. Here, we describe the development of artificial nucleobase compilation and summarized its applications in precise molecular medicine, including PCR-based diagnostics, aptamer-based diagnostics, nucleobase analogue drugs construction, ASO modification, aptamer-based therapeutics and biomaterials construction. This review provides an overview of current opportunities and challenges of artificial nucleobase-related precise molecular medicine.