Construction of nucleic acid delivery carrier using biodegradable block copolymers
| Project/Area Number |
18K18391
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 90120:Biomaterials-related
|
|---|
| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
|---|
Principal Investigator |
Hayashi Kotaro 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 研究員 (00780660)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
|
|---|
| Keywords | バイオマテリアル / 機能性高分子 / 核酸デリバリー / 核酸医薬 |
|---|
| Outline of Final Research Achievements |
Delivery systems of antisense oligonucleotides (ASOs) are expected to expand the therapeutic application of ASO medicines. To overcome the first hurdle of delivery, that is the high stability under biological environment, triblock-copolymer for ASO micelle was designed to incorporate two protective layers, hydrophilic layer and hydrophobic layer. I developed a novel poly(amino acid) based thermo-responsible polymer. Synthesized poly(amino acid) polymer exhibited a phase transition around 31 degree and a sharp transition in response to pH around neutral. I have succeeded in n synthesizing ternary polymers incorporating this dual-environment-responsive polymer toward nanomicelles formation. This polymer was expected as biocompatible materials for highly-functionalized delivery carrier design for effective accumulation into target tissues.
|
| Academic Significance and Societal Importance of the Research Achievements |
アンチセンス核酸は難治性疾患に対して、疾病の原因遺伝子のmRNAを選択的に効率よく抑制、また、病因を引き起こすスプライシング異常を改善することから、次世代の分子標的薬として期待されているが、治療応用を加速していくために標的組織や細胞への送達効率を高める技術の確立が求められている。本研究では、送達技術の第一の課題である生体内での安定性の向上を狙い、疎水層として温度応答性セグメントを組み込んだ二重保護化ミセル型ナノ粒子の開発を目的としている。また、温度応答性セグメントとカチオンにポリアミノ酸ベースの高分子を用いることで、生体内で分解性を付与し、より臨床応用を指向したデザインとなることが期待される。
|
Report
(4 results)
Research Products
(14 results)
-
-
[Journal Article] Dually stabilized triblock copolymer micelles with hydrophilic shell and hydrophobic interlayer for systemic antisense oligonucleotide delivery to solid tumor2019
Author(s)
Beob Soo Kim, Hyun Jin Kim, Shigeto Osawa, Kotaro Hayashi, Kazuko Toh, Mitsuru Naito, Hyun Su Min, Yu Yi, Ick Chan Kwon, Kazunori Kataoka, Kanjiro Miyata
-
Journal Title
ACS Biomaterials Science & Engineering
Volume: 5
Issue: 11
Pages: 5770-5780
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] Glucose-linked sub-50-nm unimer polyion complex-assembled gold nanoparticles for targeted siRNA delivery to glucose transporter 1-overexpressing breast cancer stem-like cells.2019
Author(s)
Y. Yi, H. J. Kim, M. Zheng, P. Mi, M. Naito, B. S. Kim, H. S. Min, K. Hayashi, F. Perche, K. Toh, X. Liu, Y. Mochida, H. Kinoh, H. Cabral, K. Miyata, K. Kataoka
-
Journal Title
J. Control. Release
Volume: 295
Pages: 268-277
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
