2022 Fiscal Year Final Research Report
Overhanging duplex oligonucleotide penetrating BBB
Project/Area Number |
20K21882
|
Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 90:Biomedical engineering and related fields
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
YOSHIOKA KOTARO 東京医科歯科大学, 大学院医歯学総合研究科, 特任助教 (70780641)
|
Project Period (FY) |
2020-07-30 – 2023-03-31
|
Keywords | アンチセンス核酸 / 脳血液関門 |
Outline of Final Research Achievements |
Therapeutic oligonucleotides, as the next generation of medicine following antibody therapeutics, has rapidly developed in clinical research. However, targeted organ delivery of the nucleotides has depended on the characteristics of delivery vehicles, and their toxicity remains a significant concern. The researcher has developed a novel type of double-stranded nucleic acid named overhang Double-stranded Oligonucleotide (ODO), which incorporates a protruding complementary nucleic acid strand into conventional single-stranded antisense nucleotides. The protruding nucleic acid molecule itself serves as a delivery carrier. By optimizing the chain length and nucleic acid modifications in the overhang structure, as well as discovering interchain modifications and sugar chemistry modifications that greatly enhance transferrin binding ability, researchers have successfully improved the in vivo gene inhibition effect.
|
Free Research Field |
核酸医薬
|
Academic Significance and Societal Importance of the Research Achievements |
従来の核酸医薬とは全く分子構造が異なるODOはリガンド分子を用いないトランスフェリン介在性細胞内取り込み能という革新性を有しており、本研究により中枢神経標的の核酸医薬のブレイクスルーを起こし、アルツハイマー病などの神経難病やうつ病など超高齢社会を迎えて健康寿命を脅かす神経精神疾患の根本治療開発への大きな波及効果が期待される
|