New strategy for intracellular delivery of biomacropharmaceuticals
| Project/Area Number |
15H02497
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Drug development chemistry
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
Futaki Shiroh 京都大学, 化学研究所, 教授 (50199402)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
TAKEUCHI Toshihide 京都大学, 化学研究所, 助教 (70600120)
KAWANO Kenichi 京都大学, 化学研究所, 助教 (70732874)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥47,190,000 (Direct Cost: ¥36,300,000、Indirect Cost: ¥10,890,000)
Fiscal Year 2017: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2016: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2015: ¥27,820,000 (Direct Cost: ¥21,400,000、Indirect Cost: ¥6,420,000)
|
|---|
| Keywords | 細胞内送達 / 抗体 / エンドサイトーシス / マクロピノサイトーシス / クモ毒 / 膜傷害性ペプチド / バイオ医薬品 / バイオ高分子医薬品 / エンドソーム膜不安定化ペプチド / 薬学 / 蛋白質 / 細胞 / 薬物送達 |
|---|
| Outline of Final Research Achievements |
One of the major obstacles in intracellular targeting using antibodies is their limited release from endosomes into the cytosol. We have developed an approach to deliver biomacromolecules into cells by using endosomolytic peptides derived from the cationic and membrane-lytic spider venom peptide M-lycotoxin. The delivery peptides were developed by introducing a glutamic acid into the hydrophobic face (L17E) to M-lycotoxin, enabling a marked cytosolic liberation of proteins including antibodies from endosomes. The predominant membrane-perturbation mechanism of this peptide is assumed to be the preferential disruption of negatively charged membranes (endosomal membranes) over neutral membranes (plasma membranes), and the endosomolytic peptide promotes the uptake by inducing macropinocytosis.
|
Report
(4 results)
Research Products
(20 results)
