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20231226052526.0 |
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cr uuu---uuuuu |
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231226s2023 xx |||||o 00| ||eng c |
| 024 |
7 |
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|a 10.1002/adma.202209624
|2 doi
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|a pubmed24n1172.xml
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|a (DE-627)NLM351911944
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|a (NLM)36680477
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|a DE-627
|b ger
|c DE-627
|e rakwb
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| 041 |
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|a eng
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| 100 |
1 |
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|a Lam, Kieu
|e verfasserin
|4 aut
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| 245 |
1 |
0 |
|a Unsaturated, Trialkyl Ionizable Lipids are Versatile Lipid-Nanoparticle Components for Therapeutic and Vaccine Applications
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1 |
|c 2023
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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| 338 |
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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| 500 |
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|a Date Completed 14.04.2023
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| 500 |
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|a Date Revised 14.04.2023
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2023 Genevant Sciences Corporation. Advanced Materials published by Wiley-VCH GmbH.
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|a 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
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| 650 |
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4 |
|a Journal Article
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| 650 |
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4 |
|a ionizable lipids
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| 650 |
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4 |
|a lipid nanoparticles
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| 650 |
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4 |
|a nanotechnology
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| 650 |
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4 |
|a nucleic acid
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| 650 |
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4 |
|a therapeutics
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| 650 |
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4 |
|a vaccines
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| 650 |
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7 |
|a Lipid Nanoparticles
|2 NLM
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| 650 |
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7 |
|a RNA, Small Interfering
|2 NLM
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| 650 |
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7 |
|a Lipids
|2 NLM
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| 650 |
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7 |
|a RNA, Messenger
|2 NLM
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| 700 |
1 |
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|a Leung, Ada
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Martin, Alan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wood, Mark
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Schreiner, Petra
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Palmer, Lorne
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Daly, Owen
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhao, Wenchen
|e verfasserin
|4 aut
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| 700 |
1 |
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|a McClintock, Kevin
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Heyes, James
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
|d 1998
|g 35(2023), 15 vom: 21. Apr., Seite e2209624
|w (DE-627)NLM098206397
|x 1521-4095
|7 nnns
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| 773 |
1 |
8 |
|g volume:35
|g year:2023
|g number:15
|g day:21
|g month:04
|g pages:e2209624
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| 856 |
4 |
0 |
|u http://dx.doi.org/10.1002/adma.202209624
|3 Volltext
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|a AR
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| 952 |
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|d 35
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|e 15
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