Anionic Lipid Nanoparticles Preferentially Deliver mRNA to the Hepatic Reticuloendothelial System.

Autor: Pattipeiluhu R; Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, 2333 CC, The Netherlands.; BioNanoPatterning, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, 2333 RC, The Netherlands., Arias-Alpizar G; Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, 2333 CC, The Netherlands.; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, 2333 CC, The Netherlands., Basha G; NanoMedicines Research Group, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, V6T 1Z3, Canada., Chan KYT; NanoMedicines Research Group, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, V6T 1Z3, Canada., Bussmann J; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, 2333 CC, The Netherlands., Sharp TH; BioNanoPatterning, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, 2333 RC, The Netherlands., Moradi MA; Materials and Interface Chemistry, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, Eindhoven, 5600 MB, The Netherlands., Sommerdijk N; Department of Biochemistry, Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands., Harris EN; Department of Biochemistry, University of Nebraska, Lincoln, NE, 68588, USA., Cullis PR; NanoMedicines Research Group, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, V6T 1Z3, Canada.; NanoMedicines Innovation Network (NMIN), University of British Columbia, Vancouver, V6T 1Z3, Canada.; NanoVation Therapeutics Inc., 2405 Wesbrook Mall 4th Floor, Vancouver, V6T 1Z3, Canada., Kros A; Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, 2333 CC, The Netherlands., Witzigmann D; NanoMedicines Research Group, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, V6T 1Z3, Canada.; NanoMedicines Innovation Network (NMIN), University of British Columbia, Vancouver, V6T 1Z3, Canada.; NanoVation Therapeutics Inc., 2405 Wesbrook Mall 4th Floor, Vancouver, V6T 1Z3, Canada., Campbell F; Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, 2333 CC, The Netherlands.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2022 Apr; Vol. 34 (16), pp. e2201095. Date of Electronic Publication: 2022 Mar 10.
DOI: 10.1002/adma.202201095
Abstrakt: 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.
(© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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