2022 Fiscal Year Research-status Report
Ligand-free hepatocyte-targeting of nanomedicines by selective stealth coating of liver reticuloendothelial system scavenger cells
| Project/Area Number |
21K18062
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| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
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Principal Investigator |
ディリサラ アンジャネユル 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 (70794353)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | Hepatocytes / Kupffer cells / Sinusoidal endothelium / Ligands / Nanomedicine |
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| Outline of Annual Research Achievements |
Site-specific delivery of nanomedicines to liver parenchymal hepatocytes is a potential strategy for treating various liver diseases. However, the rapid elimination of nanomedicines from the bloodstream by the liver reticuloendothelial cells upon systemic administration is critical in clinical translation because it decreases the delivery efficiency to hepatocytes. To solve this, we stealth-coated scavenger cells using two-armed PEG-conjugated oligo(L-ornithine) (2-arm-PEG-OligoOrn). 2-arm-PEG-OligoOrn was progressively cleared from sinusoidal walls to bile, resulting in the transient coating. Such coating effectively prevented sinusoidal clearance of nonviral and viral gene vectors, thereby boosting their gene transfection efficiency in the hepatocytes.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We employed a liposomal mRNA delivery system that is in the human clinical trial.
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| Strategy for Future Research Activity |
Instead of developing new nanomedicines, we will focus on redirecting FDA-approved nanomedicines from the liver scavenger cells to liver parenchymal hepatocytes without decorating specific ligands. In the future, such hepatocyte-selective protein expression will be exploited to develop a cure for chronic hepatitis B by destroying the virus's persistent covalently closed circular (ccc)DNA using a gene-editing tool, clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9.
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| Causes of Carryover |
We will buy antibodies, messenger RNA, and labeling reagents.
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