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Artificial nucleic acids have recently been widely used with their properties optimized for various technologies such as the inhibition of gene expression (antisense/antigene strategies, RNA interference) and genetic diagnosis (single nucleotide polymorphism (SNP), damaged nucleobase). For practical application of nucleic acid therapeutics, establishment of an effective delivery system for oligonucleotides is also required because of their poor permeability into cells. Various useful delivery technologies including lipoplexes formed using cationic lipids and polyplexes made with cationic polymers have been developed; however, there is no crucial tool for oligonucleotide therapeutics at present. If technologies of functional nucleic acids and adequate delivery systems are cooperatively developed, the realization of nucleic acid therapeutics might be effectively accelerated. Based on this concept, we have been cooperatively developing these technologies based on organic synthetic chemistry during the past decade. This paper summarizes our recent results: 1) development of a specific fluorescent probe for 8-oxoguanine; 2) synthesis and evaluation of a prodrug-type small interfering RNA (siRNA) molecule; and 3) targeted intracellular delivery of oligonucleotides via conjugation with receptor-targeted ligands.

Development of Artificial Nucleic Acids Functionalized for Damaged Gene Diagnosis, Gene Inhibition and Delivery System