Lipid nanoparticle mRNA systems containing high levels of sphingomyelin engender higher protein expression in hepatic and extra-hepatic tissues.
bone marrow
helper lipids
hepatocytes
lipid nanoparticles
mRNA
splenocytes
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
14 Sep 2023
14 Sep 2023
Historique:
received:
21
12
2022
accepted:
08
06
2023
medline:
11
8
2023
pubmed:
11
8
2023
entrez:
11
8
2023
Statut:
epublish
Résumé
Lipid nanoparticles (LNPs) for delivery of mRNA usually contain ionizable lipid/helper lipid/cholesterol/PEG-lipid in molar ratios of 50:10:38.5:1.5, respectively. These LNPs are rapidly cleared from the circulation following intravenous (i.v.) administration, limiting uptake into other tissues. Here, we investigate the properties of LNP mRNA systems prepared with high levels of "helper" lipids such as 1,2-distearoyl-sn-glycero-3-phosphorylcholine (DSPC) or N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine (egg sphingomyelin [ESM]). We show that LNP mRNAs containing 40 mol % DSPC or ESM have a unique morphology with a small interior "solid" core situated in an aqueous compartment that is bounded by a lipid bilayer. The encapsulated mRNA exhibits enhanced stability in the presence of serum. LNP mRNA systems containing 40 mol % DSPC or ESM exhibit significantly improved transfection properties
Identifiants
pubmed: 37564393
doi: 10.1016/j.omtm.2023.06.005
pii: S2329-0501(23)00095-5
pmc: PMC10410000
doi:
Types de publication
Journal Article
Langues
eng
Pagination
235-245Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
P.R.C. has financial interests in Acuitas Therapeutics, Mesentech, and NanoVation Therapeutics. D.W. has financial interests in NanoVation Therapeutics.
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