Unsaturated, Trialkyl Ionizable Lipids are Versatile Lipid-Nanoparticle Components for Therapeutic and Vaccine Applications

Unsaturated, Trialkyl Ionizable Lipids are Versatile Lipid-Nanoparticle Components for Therapeutic and Vaccine Applications

© 2023 Genevant Sciences Corporation. Advanced Materials published by Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 15 vom: 21. Apr., Seite e2209624
1. Verfasser: Lam, Kieu (VerfasserIn)
Weitere Verfasser: Leung, Ada, Martin, Alan, Wood, Mark, Schreiner, Petra, Palmer, Lorne, Daly, Owen, Zhao, Wenchen, McClintock, Kevin, Heyes, James
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article ionizable lipids lipid nanoparticles nanotechnology nucleic acid therapeutics vaccines Lipid Nanoparticles RNA, Small Interfering Lipids RNA, Messenger
Beschreibung
Zusammenfassung:© 2023 Genevant Sciences Corporation. Advanced Materials published by Wiley-VCH GmbH.
Lipid nanoparticles (LNPs) have proven a successful platform for the delivery of nucleic acid (NA)-based therapeutics and vaccines, with the ionizable lipid component playing a key role in modulating potency and tolerability. Here, a library of 16 novel ionizable lipids is screened hypothesizing that short, branched trialkyl hydrophobic domains can improve LNP fusogenicity or endosomal escape, and potency. LNPs formulated with the top-performing trialkyl lipid (Lipid 10) encapsulating transthyretin siRNA elicit significantly greater gene silencing and are better tolerated than those with the benchmark Onpattro lipid DLin-MC3-DMA. Lipid 10 also demonstrates superior liver delivery of mRNA when compared to other literature ionizable lipids, is well tolerated, and successfully repeat-doses in nonhuman primates. In a prime-boost hemagglutinin rodent vaccine model, intramuscular administration of Lipid-10 LNP elicits comparable or better antibody titers to the SM-102 and ALC-0315 lipid compositions used in the U.S. Food and Drug Administration approved mRNA COVID vaccines. These data suggest that Lipid 10 is a particularly versatile ionizable lipid, well-suited for both systemic therapeutic and intramuscular vaccine applications and able to successfully deliver diverse NA payloads
Beschreibung:Date Completed 14.04.2023
Date Revised 14.04.2023
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202209624