Anionic Lipid Nanoparticles Preferentially Deliver mRNA to the Hepatic Reticuloendothelial System

Anionic Lipid Nanoparticles Preferentially Deliver mRNA to the Hepatic Reticuloendothelial System

© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 34(2022), 16 vom: 02. Apr., Seite e2201095
1. Verfasser: Pattipeiluhu, Roy (VerfasserIn)
Weitere Verfasser: Arias-Alpizar, Gabriela, Basha, Genc, Chan, Karen Y T, Bussmann, Jeroen, Sharp, Thomas H, Moradi, Mohammad-Amin, Sommerdijk, Nico, Harris, Edward N, Cullis, Pieter R, Kros, Alexander, Witzigmann, Dominik, Campbell, Frederick
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article embryonic zebrafish lipid nanoparticles mRNA delivery reticuloendothelial system stabilin-2 Lipid Nanoparticles Lipids Liposomes RNA, Messenger RNA, Small Interfering
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520 |a 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 
650 4 |a Journal Article 
650 4 |a embryonic zebrafish 
650 4 |a lipid nanoparticles 
650 4 |a mRNA delivery 
650 4 |a reticuloendothelial system 
650 4 |a stabilin-2 
650 7 |a Lipid Nanoparticles  |2 NLM 
650 7 |a Lipids  |2 NLM 
650 7 |a Liposomes  |2 NLM 
650 7 |a RNA, Messenger  |2 NLM 
650 7 |a RNA, Small Interfering  |2 NLM 
700 1 |a Arias-Alpizar, Gabriela  |e verfasserin  |4 aut 
700 1 |a Basha, Genc  |e verfasserin  |4 aut 
700 1 |a Chan, Karen Y T  |e verfasserin  |4 aut 
700 1 |a Bussmann, Jeroen  |e verfasserin  |4 aut 
700 1 |a Sharp, Thomas H  |e verfasserin  |4 aut 
700 1 |a Moradi, Mohammad-Amin  |e verfasserin  |4 aut 
700 1 |a Sommerdijk, Nico  |e verfasserin  |4 aut 
700 1 |a Harris, Edward N  |e verfasserin  |4 aut 
700 1 |a Cullis, Pieter R  |e verfasserin  |4 aut 
700 1 |a Kros, Alexander  |e verfasserin  |4 aut 
700 1 |a Witzigmann, Dominik  |e verfasserin  |4 aut 
700 1 |a Campbell, Frederick  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Advanced materials (Deerfield Beach, Fla.)  |d 1998  |g 34(2022), 16 vom: 02. Apr., Seite e2201095  |w (DE-627)NLM098206397  |x 1521-4095  |7 nnns 
773 1 8 |g volume:34  |g year:2022  |g number:16  |g day:02  |g month:04  |g pages:e2201095 
856 4 0 |u http://dx.doi.org/10.1002/adma.202201095  |3 Volltext 
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