Heteroduplex Oligonucleotides - 新しい核酸医薬プラットフォームとしての可能性 -

抄録

Nucleic acid medicines represented by antisense oligonucleotides (ASO) and siRNA have been attracting attention as a new modality to treat genetic disorders and intractable diseases. To date, 17 drugs in this modality have been approved.  A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties such as increased resistance to nuclease and improved target binding affinity. The toxicity associated with chemical modification and efficient delivery to target tissues are the major hurdles remaining for further application of nucleic acid medicines to a wider range of disorders.

　Heteroduplex oligonucleotides (HDO) is a platform technology which could be applied to solve these issues. HDO has the features of DNA/RNA or DNA/DNA double-stranded oligonucleotide consisting of the ASO strand and a complementary sequence to the ASO as carrier strand which is conjugated with specific ligands. Ligand-molecules can work to deliver HDO to the target tissues. Now, research and development based on HDO is actively underway as a new modality that improves overall drug discovery potentials. Toxicity reduction and efficient delivery are the critical elements to be realized in the HDO format by utilizing the characteristics of double stranded structure and introducing suitable ligands.

　In this presentation, current status and issues for nucleic acid medicines are summarized and expecting future approaches are discussed with referring to the HDO technology.