Project/Area Number |
15K16335
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Biomedical engineering/Biomaterial science and engineering
|
Research Institution | National Cardiovascular Center Research Institute |
Principal Investigator |
Kambe Yusuke 国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (30747671)
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
|
Keywords | キメラタンパク / メタボリックスイッチング / DDS / DNCS / バイオマテリアル |
Outline of Final Research Achievements |
In the drug-navigated clearance system, a drug called “navigator” needs to be synthesized to switch the metabolic pathway of an etiologic agent. Here, dialysis-related amyloidosis was used as a model disease and its etiologic agent, beta 2-microglubulin (b2MG), was targeted to switch its metabolic pathway from the kidney to the liver. A navigator composed a capturing part and a navigating part was developed as a chimeric protein, and its functions were evaluated. In vitro, immunoprecipitation and competitive inhibition assays showed that the navigator captured b2MG and bound to LDL-receptor, which is highly expressed on hepatocytes, respectively. Additionally, the removal of b2MG from the culture medium of hepatocytes by the navigator was shown in an ELISA. Although the navigator accumulated in the liver when injected intravenously, the body distribution of b2MG in mice unchanged regardless of the introduction of the navigator. In vivo functions of the navigator need to be enhanced.
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