Anionic Lipid Nanoparticles Preferentially Deliver mRNA to the Hepatic Reticuloendothelial System
| Autor: | Roy Pattipeiluhu, Gabriela Arias‐Alpizar, Genc Basha, Karen Y. T. Chan, Jeroen Bussmann, Thomas H. Sharp, Mohammad‐Amin Moradi, Nico Sommerdijk, Edward N. Harris, Pieter R. Cullis, Alexander Kros, Dominik Witzigmann, Frederick Campbell |
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| Přispěvatelé: | Materials and Interface Chemistry |
| Rok vydání: | 2022 |
| Předmět: |
Liver/metabolism
RNA Messenger/metabolism Messenger/metabolism lipid nanoparticles Mice mRNA delivery Animals General Materials Science Tissue Distribution RNA Messenger RNA Small Interfering Mononuclear Phagocyte System Zebrafish reticuloendothelial system RNA Small Interfering/genetics Mechanical Engineering Lipids Mononuclear Phagocyte System/metabolism embryonic zebrafish Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] Liver Small Interfering/genetics Mechanics of Materials Liposomes RNA stabilin-2 Nanoparticles |
| Zdroj: | Advanced Materials, 34 Advanced Materials Advanced Materials, 34(16):2201095. Wiley-VCH Verlag Advanced Materials, 34(16):2201095 Advanced Materials, 34, 16 Advanced Materials, 34(16). WILEY-V C H VERLAG GMBH |
| ISSN: | 0935-9648 |
| Popis: | Contains fulltext : 282460.pdf (Publisher’s version ) (Open Access) Lipid nanoparticles (LNPs) are the leading nonviral technologies for the delivery of exogenous RNA to target cells in vivo. As systemic delivery platforms, these technologies are exemplified by Onpattro, an approved LNP-based RNA interference therapy, administered intravenously and targeted to parenchymal liver cells. The discovery of systemically administered LNP technologies capable of preferential RNA delivery beyond hepatocytes has, however, proven more challenging. Here, preceded by comprehensive mechanistic understanding of in vivo nanoparticle biodistribution and bodily clearance, an LNP-based messenger RNA (mRNA) delivery platform is rationally designed to preferentially target the hepatic reticuloendothelial system (RES). Evaluated in embryonic zebrafish, validated in mice, and directly compared to LNP-mRNA systems based on the lipid composition of Onpattro, RES-targeted LNPs significantly enhance mRNA expression both globally within the liver and specifically within hepatic RES cell types. Hepatic RES targeting requires just a single lipid change within the formulation of Onpattro to switch LNP surface charge from neutral to anionic. This technology not only provides new opportunities to treat liver-specific and systemic diseases in which RES cell types play a key role but, more importantly, exemplifies that rational design of advanced RNA therapies must be preceded by a robust understanding of the dominant nano-biointeractions involved. |
| Databáze: | OpenAIRE |
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