A Potent Branched-Tail Lipid Nanoparticle Enables Multiplexed mRNA Delivery and Gene Editing
gene editing
lipid nanoparticles
lipidoid
liver delivery
mRNA delivery
protein expression
Journal
Nano letters
ISSN: 1530-6992
Titre abrégé: Nano Lett
Pays: United States
ID NLM: 101088070
Informations de publication
Date de publication:
08 07 2020
08 07 2020
Historique:
pubmed:
5
6
2020
medline:
25
6
2021
entrez:
5
6
2020
Statut:
ppublish
Résumé
The clinical translation of messengerRNA (mRNA) drugs has been slowed by a shortage of delivery vehicles that potently and safely shuttle mRNA into target cells. Here, we describe the properties of a particularly potent branched-tail lipid nanoparticle that delivers mRNA to >80% of three major liver cell types. We characterize mRNA delivery spatially, temporally, and as a function of injection type. Following intravenous delivery, our lipid nanoparticle induced greater protein expression than two benchmark lipids, C12-200 and DLin-MC3-DMA, at an mRNA dose of 0.5 mg/kg. Lipid nanoparticles were sufficiently potent to codeliver three distinct mRNAs (firefly luciferase, mCherry, and erythropoietin) and, separately, Cas9 mRNA and single guide RNA (sgRNA) for proof-of-concept nonviral gene editing in mice. Furthermore, our branched-tail lipid nanoparticle was neither immunogenic nor toxic to the liver. Together, these results demonstrate the unique potential of this lipid material to improve the management of diseases rooted in liver dysfunction.
Identifiants
pubmed: 32496069
doi: 10.1021/acs.nanolett.0c00596
pmc: PMC7781386
mid: NIHMS1655840
doi:
Substances chimiques
Lipids
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5167-5175Subventions
Organisme : NIBIB NIH HHS
ID : F32 EB029345
Pays : United States
Références
Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E1941-E1950
pubmed: 28202722
Small. 2019 Feb;15(6):e1805097
pubmed: 30637934
Nat Biotechnol. 2017 Nov 9;35(11):995-997
pubmed: 29121028
Angew Chem Int Ed Engl. 2016 Oct 24;55(44):13808-13812
pubmed: 27690187
AAPS J. 2012 Sep;14(3):559-70
pubmed: 22619041
Nat Commun. 2014 Jun 27;5:4277
pubmed: 24969323
Clin Diagn Lab Immunol. 2005 Jan;12(1):60-7
pubmed: 15642986
Langmuir. 2011 Mar 1;27(5):1907-14
pubmed: 21250743
Angew Chem Int Ed Engl. 2016 Aug 8;55(33):9591-5
pubmed: 27376704
Mol Ther. 2018 Mar 7;26(3):814-821
pubmed: 29428299
Nano Lett. 2015 Nov 11;15(11):7300-6
pubmed: 26469188
Gene Ther. 2016 Oct;23(10):699-707
pubmed: 27356951
Nano Lett. 2015 Dec 9;15(12):8099-107
pubmed: 26529392
Nat Neurosci. 2010 Jan;13(1):133-40
pubmed: 20023653
Sci Rep. 2019 Jun 19;9(1):8760
pubmed: 31217430
Adv Mater. 2016 Apr 20;28(15):2939-43
pubmed: 26889757
Mol Ther. 2018 Mar 7;26(3):801-813
pubmed: 29433939
Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):3955-60
pubmed: 24516150
Compr Physiol. 2013 Apr;3(2):785-97
pubmed: 23720329
World J Gastroenterol. 2017 Nov 21;23(43):7666-7677
pubmed: 29209108
Cell. 2017 Mar 9;168(6):1114-1125.e10
pubmed: 28222903
Expert Opin Biol Ther. 2014 Feb;14(2):183-95
pubmed: 24328708
Mol Ther. 2013 Aug;21(8):1570-8
pubmed: 23799535
J Am Assoc Lab Anim Sci. 2011 Sep;50(5):600-13
pubmed: 22330705
J Cancer Res Clin Oncol. 2018 Feb;144(2):309-320
pubmed: 29288362
Angew Chem Int Ed Engl. 2012 Aug 20;51(34):8529-33
pubmed: 22782619
Angew Chem Int Ed Engl. 2017 Oct 23;56(44):13709-13712
pubmed: 28925033
Nat Biotechnol. 2016 Mar;34(3):328-33
pubmed: 26829318
J Diabetes Res. 2018 Jul 4;2018:1205121
pubmed: 30116732
Oncotarget. 2017 Jun 27;8(41):69577-69593
pubmed: 29050226
Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E448-E456
pubmed: 28069945
Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):E3351-E3360
pubmed: 29588418
Nano Lett. 2016 Feb 10;16(2):842-8
pubmed: 26727632
Nat Commun. 2018 Oct 29;9(1):4493
pubmed: 30374059
Adv Mater. 2019 Oct;31(43):e1902798
pubmed: 31429126
Cell Res. 2017 Mar;27(3):440-443
pubmed: 28117345
Cell Stem Cell. 2010 Nov 5;7(5):618-30
pubmed: 20888316
J Gastrointest Oncol. 2016 Feb;7(1):45-57
pubmed: 26941983
Angew Chem Int Ed Engl. 2017 Jan 19;56(4):1059-1063
pubmed: 27981708
Science. 2009 Sep 4;325(5945):1246-50
pubmed: 19644074
Toxicol Appl Pharmacol. 2016 May 15;299:70-7
pubmed: 26773813