Synthetic mRNA rescues very long-chain acyl-CoA dehydrogenase deficiency in patient fibroblasts and a murine model.

Humans Animals Mice Acyl-CoA Dehydrogenase, Long-Chain RNA, Messenger / genetics Disease Models, Animal Fibroblasts / metabolism Lipid Metabolism, Inborn Errors / genetics
Acadvl(-/-) mouse Fatty acid β-oxidation Fibroblasts Synthetic mRNA Very long-chain acyl-CoA dehydrogenase deficiency

Journal

Molecular genetics and metabolism
ISSN: 1096-7206
Titre abrégé: Mol Genet Metab
Pays: United States
ID NLM: 9805456

Informations de publication

Date de publication:
01 2023
Historique:
received: 21 12 2022
accepted: 21 12 2022
pmc-release: 01 01 2024
pubmed: 30 12 2022
medline: 28 1 2023
entrez: 29 12 2022
Statut: ppublish

Résumé

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inborn error of long chain fatty acid β-oxidation (FAO) with limited treatment options. Patients present with heterogeneous clinical phenotypes affecting predominantly heart, liver, and skeletal muscle. While VLCAD deficiency is a systemic disease, restoration of liver FAO has the potential to improve symptoms more broadly due to increased total body ATP production and reduced accumulation of potentially toxic metabolites. We explored the use of synthetic human VLCAD (hVLCAD) mRNA and lipid nanoparticle encapsulated hVLCAD mRNA (LNP-VLCAD) to generate functional VLCAD enzyme in patient fibroblasts derived from VLCAD deficient patients, mouse embryonic fibroblasts, hepatocytes isolated from VLCAD knockout (Acadvl

Identifiants

DOI: 10.1016/j.ymgme.2022.106982 PMID: 36580829 PMC: PMC9877169
pubmed: 36580829
pii: S1096-7192(22)00460-7
doi: 10.1016/j.ymgme.2022.106982
pmc: PMC9877169
mid: NIHMS1861178
pii:
doi:

Substances chimiques

Acyl-CoA Dehydrogenase, Long-Chain EC 1.3.8.8
RNA, Messenger 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

106982

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK078775
Pays : United States

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Moderna Therapeutic, Inc. provided the experimental treatment and funded the study. All authors from University of Pittsburgh have no conflict of interest.

Références

Am J Physiol Heart Circ Physiol. 2006 Mar;290(3):H1289-97
pubmed: 16199475
Mol Genet Metab. 2011 Apr;102(4):418-29
pubmed: 21237683
Biomaterials. 2016 Dec;109:78-87
pubmed: 27680591
J Inherit Metab Dis. 2010 Oct;33(5):527-32
pubmed: 20449660
J Control Release. 2015 Nov 10;217:345-51
pubmed: 26264835
Genet Med. 2021 May;23(5):816-829
pubmed: 33495527
Gut. 2019 Jul;68(7):1323-1330
pubmed: 30796097
Curr Protoc Hum Genet. 2010 Jan;Chapter 17:Unit 17.8.1-20
pubmed: 20063265
Methods Enzymol. 2000;324:241-58
pubmed: 10989435
Hum Mol Genet. 2019 Mar 15;28(6):928-941
pubmed: 30445591
Nano Lett. 2015 Nov 11;15(11):7300-6
pubmed: 26469188
J Biol Chem. 2019 Aug 16;294(33):12380-12391
pubmed: 31235473
J Inherit Metab Dis. 2010 Oct;33(5):539-46
pubmed: 20532823
Am J Hum Genet. 2019 Apr 4;104(4):625-637
pubmed: 30879639
Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E1941-E1950
pubmed: 28202722
Nature. 2010 Mar 4;464(7285):121-5
pubmed: 20203611
N Engl J Med. 2000 Jun 22;342(25):1866-70
pubmed: 10861321
Mol Genet Metab. 2016 Aug;118(4):272-81
pubmed: 27209629
Am J Manag Care. 2020 Aug;26(7 Suppl):S147-S154
pubmed: 32840329
J Biol Chem. 2010 Sep 24;285(39):29834-41
pubmed: 20663895
Cells. 2021 May 18;10(5):
pubmed: 34069977
Pediatr Res. 2008 Jun;63(6):632-7
pubmed: 18317232
J Inherit Metab Dis. 2021 Jan;44(1):253-263
pubmed: 32885845
Front Genet. 2021 Jan 15;11:598760
pubmed: 33584796
Mol Genet Metab. 2021 Sep-Oct;134(1-2):156-163
pubmed: 34556413
Cell Rep. 2017 Dec 19;21(12):3548-3558
pubmed: 29262333
Circ Res. 2003 Sep 5;93(5):448-55
pubmed: 12893739
Biosci Rep. 2015 Nov 20;36(1):e00281
pubmed: 26589966
Curr Protoc Mol Biol. 2005 May;Chapter 28:Unit 28.1
pubmed: 18265366
Am J Hum Genet. 2007 Jul;81(1):87-103
pubmed: 17564966
Nat Med. 2018 Dec;24(12):1899-1909
pubmed: 30297912
Mol Ther. 2018 Jun 6;26(6):1509-1519
pubmed: 29653760
FEBS J. 2006 Dec;273(23):5288-302
pubmed: 17059463
Hum Mol Genet. 2001 Sep 15;10(19):2069-77
pubmed: 11590124
Methods Mol Biol. 2010;633:185-96
pubmed: 20204628
J Clin Invest. 1995 Jun;95(6):2465-73
pubmed: 7769092
Mol Genet Metab. 2005 May;85(1):7-11
pubmed: 15862275
Cytotechnology. 2012 Mar;64(2):187-95
pubmed: 22105762
Eur J Clin Invest. 2004 Mar;34(3):191-6
pubmed: 15025677
Nature. 1997 May 1;387(6628):90-4
pubmed: 9139827
FEBS J. 2018 Apr;285(8):1437-1455
pubmed: 29476646
Sci Adv. 2020 Jun 24;6(26):eaaz6893
pubmed: 32637598
Clin Transl Immunology. 2021 Jun 27;10(6):e1304
pubmed: 34194748
Mol Ther. 2012 Jun;20(6):1131-8
pubmed: 22395529
Biochem Biophys Rep. 2016 Sep 17;8:333-339
pubmed: 28955973
Circulation. 1999 Nov 30;100(22):2248-53
pubmed: 10577999
J Inherit Metab Dis. 2013 Sep;36(5):795-803
pubmed: 23053472
Hum Gene Ther. 2019 Oct;30(10):1180-1189
pubmed: 31179759
Nat Commun. 2017 Mar 02;8:14630
pubmed: 28251988

Auteurs

Xue-Jun Zhao (XJ)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.

Ai-Walid Mohsen (AW)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.

Stephanie Mihalik (S)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.

Keaton Solo (K)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.

Ermal Aliu (E)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.

Huifang Shi (H)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.

Shakuntala Basu (S)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.

Catherine Kochersperger (C)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.

Clinton Van't Land (C)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.

Anuradha Karunanidhi (A)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.

Kimberly A Coughlan (KA)

Moderna Therapeutics, Inc., Rare Diseases, 200 Technology Square, Cambridge, MA, USA.

Summar Siddiqui (S)

Moderna Therapeutics, Inc., Rare Diseases, 200 Technology Square, Cambridge, MA, USA.

Lisa M Rice (LM)

Moderna Therapeutics, Inc., Rare Diseases, 200 Technology Square, Cambridge, MA, USA.

Shawn Hillier (S)

Moderna Therapeutics, Inc., Rare Diseases, 200 Technology Square, Cambridge, MA, USA.

Eleonora Guadagnin (E)

Moderna Therapeutics, Inc., Rare Diseases, 200 Technology Square, Cambridge, MA, USA.

Paloma H Giangrande (PH)

Moderna Therapeutics, Inc., Rare Diseases, 200 Technology Square, Cambridge, MA, USA.

Paolo G V Martini (PGV)

Moderna Therapeutics, Inc., Rare Diseases, 200 Technology Square, Cambridge, MA, USA.

Jerry Vockley (J)

Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: vockleyg@upmc.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Synthetic mRNA rescues very long-chain...
questionsmedicales.fr › Eucaryotes › Animaux › Synthetic mRNA rescues very long-chain...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Synthetic mRNA rescues very long-chain...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Flavoprotéines › Long-chain-acyl-CoA dehydrogenase › Synthetic mRNA rescues very long-chain...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Synthetic mRNA rescues very long-chain...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Synthetic mRNA rescues very long-chain...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Synthetic mRNA rescues very long-chain...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Erreurs innées du métabolisme › Erreurs innées du métabolisme lipidique › Synthetic mRNA rescues very long-chain...