Biodistribution of Lipid 5, mRNA, and Its Translated Protein Following Intravenous Administration of mRNA-Encapsulated Lipid Nanoparticles in Rats.

Rats Male Female Animals Rats, Sprague-Dawley Tissue Distribution Chromatography, Liquid Rats, Long-Evans RNA, Messenger / genetics Xenobiotics Tandem Mass Spectrometry Infusions, Intravenous Nanoparticles Lipids / chemistry RNA, Small Interfering / chemistry

Journal

Drug metabolism and disposition: the biological fate of chemicals
ISSN: 1521-009X
Titre abrégé: Drug Metab Dispos
Pays: United States
ID NLM: 9421550

Informations de publication

Date de publication:
Jul 2023
Historique:
received: 08 06 2022
accepted: 05 04 2023
medline: 19 6 2023
pubmed: 20 5 2023
entrez: 19 5 2023
Statut: ppublish

Résumé

RNA-based therapeutics and vaccines represent a novel and expanding class of medicines, the success of which depends on the encapsulation and protection of mRNA molecules in lipid nanoparticle (LNP)-based carriers. With the development of mRNA-LNP modalities, which can incorporate xenobiotic constituents, extensive biodistribution analyses are necessary to better understand the factors that influence their in vivo exposure profiles. This study investigated the biodistribution of heptadecan-9-yl 8-((2-hydroxyethyl)(8-(nonyloxy)-8-oxooctyl)amino)octanoate (Lipid 5)-a xenobiotic amino lipid-and its metabolites in male and female pigmented (Long-Evans) and nonpigmented (Sprague Dawley) rats by using quantitative whole-body autoradiography (QWBA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques. After intravenous injection of Lipid 5-containing LNPs,

Identifiants

DOI: 10.1124/dmd.122.000980 PMID: 37208184
pubmed: 37208184
pii: dmd.122.000980
doi: 10.1124/dmd.122.000980
doi:

Substances chimiques

Lipid Nanoparticles 0
RNA, Messenger 0
Xenobiotics 0
Lipids 0
RNA, Small Interfering 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

813-823

Informations de copyright

Copyright © 2023 by The Author(s).

Auteurs

Lei Ci (L)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Marjie Hard (M)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Hannah Zhang (H)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Srujan Gandham (S)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Serenus Hua (S)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

John Wickwire (J)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Tod Wehrman (T)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Richard Slauter (R)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Andrew Auerbach (A)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Matthew Kenney (M)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Greg Mercer (G)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Tracy Hendrick (T)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Örn Almarsson (Ö)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Eugene Cheung (E)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.).

Douglas Burdette (D)

Moderna, Inc., Cambridge, Massachusetts (L.C., H.Z., S.G., S.H., J.W., A.A., M.K., G.M., E.C., D.B.); Praxis Precision Medicines, Boston, Massachusetts (M.H.); Charles River Laboratories, Mattawan, Michigan (T.W., R.S.); Duke University, Durham, North Carolina (T.H.); and Lyndra Therapeutics, Cambridge, Massachusetts (O.A.) Doug.Burdette@modernatx.com.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Eucaryotes › Animaux › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Sprague-Dawley › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Pharmacocinétique › Distribution tissulaire › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Techniques d'investigation › Techniques de chimie analytique › Chromatographie › Chromatographie en phase liquide › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Long-Evans › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Préparations pharmaceutiques › Xénobiotique › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Techniques d'investigation › Techniques de chimie analytique › Spectrométrie de masse › Spectrométrie de masse en tandem › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Perfusions parentérales › Perfusions veineuses › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Nanoparticules › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Lipides › Biodistribution of Lipid 5, mRNA, and Its...
Recherchemedicale.com › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › Petit ARN interférent › Biodistribution of Lipid 5, mRNA, and Its...