Development of Artificial Nucleic Acids Targeting Non-Coding DNA

　In recent years, chemical modifications of DNA have been recognized as key regulators of epigenetic mechanisms that control gene expression without altering the underlying DNA sequence. Among these modifications, 5-formylcytosine (5fC) was originally identified as an intermediate generated during the active demethylation of methylated DNA. Nevertheless, many aspects of its chemical properties and physiological roles remain poorly understood, highlighting the need for novel analytical tools. To address this challenge, we focused on photo-responsive molecular probes, whose reactivity can be controlled by external light stimuli. Based on this concept, we developed a novel photo-responsive oligonucleotide, termed GPs-Oligo. We found that GPs-Oligo undergoes a selective photo-crosslinking reaction with 5fC upon UV irradiation and exhibits reactivity distinct from that toward other cytosine modifications. Furthermore, we constructed a DNA microarray platform incorporating GPs-Oligo and established a technological basis for a diagnostic chip capable of selectively detecting 5fC.
  On the other hand, despite the remarkable progress and growing interest in nucleic acid therapeutics, the development of efficient drug delivery systems (DDS) has remained one of the most formidable challenges to their practical application. To address these challenges, we have developed a unique drug delivery system based on extracellular vesicles (EVs), particularly exosomes. I this report, we will also discuss a novel DDS strategy in which nucleic acid therapeutics are delivered into cells by hijacking exosomes.