| Project/Area Number |
21K18062
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
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Principal Investigator |
Dirisala Anjaneyulu 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, 主任研究員 (70794353)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | Liver blockade / Sinusoidal endothelium / Kupffer cells / Nanomedicine retargeting / Liver sinusoidal coating / Liver stealth coating / Hepatocyte targeting / Gene delivery / Hepatocytes / Genome editing / CRISPR/Cas9 / Gene drugs |
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| Outline of Research at the Start |
Hepatocyte-selective delivery of nanomedicines is a potential strategy for treating liver diseases. However, liver scavenger cells eliminate most of the injected dose before reaching hepatocytes. Research will be focused on minimizing this nonspecific uptake to maximize hepatocyte-directed delivery.
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| Outline of Final Research Achievements |
Site-specific delivery of nucleic acid therapeutics to liver parenchymal cells (hepatocytes) is a potential strategy for the treatment of many liver diseases. However, the biggest issue in hepatocyte-selective delivery of systemically administered nucleic acid therapeutics is nonspecific elimination by liver scavenger reticuloendothelial system (RES) [sinusoidal endothelial cells (SECs) and Kupffer cells (KCs)], causing a substantial decrease in delivery efficiency. In this study, we addressed this issue by selective masking of scavenger receptors of RES with PEG coating using a oligocation conjugated two-armed poly(ethylene glycol) to suppress the recognition and elimination of nucleic acid therapeutics by liver RES and thereby maximizing the delivery to hepatocytes.
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| Academic Significance and Societal Importance of the Research Achievements |
Scientific significance: We developed in situ stealth coating technology for transient blockade of liver scavenger cells, and promoted nucleic acid therapeutic transfection.
Social significance: Our technology can increase the therapeutic potential of nanomedicines with lower doses without ligands.
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