Abstract
The prospect of developing novel oligonucleotide therapeutics through the practical use of mRNA vaccines during the COVID-19 pandemic are increasing rapidly. Because most of the proteins and nucleic acids that are targets of oligonucleotide therapeutics, such as antisense oligonucleotides, aptamers, and CpG oligodeoxynucleotides, localize inside cells, it is important to control the interaction between oligonucleotides and their target molecules in the intracellular environment to ensure proper function. The structural flexibility of oligonucleotides is higher than that of small chemical compounds and proteins; oligonucleotides change their structure and topology depending on the nucleotide sequence and surrounding conditions. The guanine quadruplex structure, formed by guanine-rich oligonucleotides, dynamically changes its structure in response to the surrounding conditions, and plays an important role in regulating cellular function. In this paper, we review the fundamental characteristics of the guanine quadruplex structure, and methods for analyzing the topology of oligonucleotides, and introduce the application of guanine quadruplex-based oligonucleotide to novel oligonucleotides therapeutics.