Endosomal escape: A bottleneck for LNP-mediated therapeutics.
LNPs
RNA vaccines and therapeutics
endo-lysosomes
endosomal escape
mRNA
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
12 Mar 2024
12 Mar 2024
Historique:
medline:
6
3
2024
pubmed:
4
3
2024
entrez:
4
3
2024
Statut:
ppublish
Résumé
Lipid nanoparticles (LNPs) have recently emerged as a powerful and versatile clinically approved platform for nucleic acid delivery, specifically for mRNA vaccines. A major bottleneck in the field is the release of mRNA-LNPs from the endosomal pathways into the cytosol of cells where they can execute their encoded functions. The data regarding the mechanism of these endosomal escape processes are limited and contradicting. Despite extensive research, there is no consensus regarding the compartment of escape, the cause of the inefficient escape and are currently lacking a robust method to detect the escape. Here, we review the currently known mechanisms of endosomal escape and the available methods to study this process. We critically discuss the limitations and challenges of these methods and the possibilities to overcome these challenges. We propose that the development of currently lacking robust, quantitative high-throughput techniques to study endosomal escape is timely and essential. A better understanding of this process will enable better RNA-LNP designs with improved efficiency to unlock new therapeutic modalities.
Identifiants
pubmed: 38437552
doi: 10.1073/pnas.2307800120
doi:
Substances chimiques
RNA
63231-63-0
RNA, Messenger
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2307800120Subventions
Organisme : EC | European Research Council (ERC)
ID : 101055029
Organisme : Israel Science Foundation (ISF)
ID : 2012/20
Déclaration de conflit d'intérêts
Competing interests statement:D.P. receives licensing fees (to patents on which he was an inventor) from, invested in, consults (or on scientific advisory boards or boards of directors) for, lectured (and received a fee), or conducts sponsored research at TAU for the following entities: ART Biosciences, BioNtech SE, Eleven Therapeutics, Kernal Biologics, Merck, Newphase Ltd., NeoVac Ltd., RiboX Therapeutics, Roche, SirTLabs Corporation, and Teva Pharmaceuticals Inc. All other authors declare no competing financial interests.
Références
J Vis Exp. 2018 May 25;(135):
pubmed: 29889208
Nat Biotechnol. 2013 Jul;31(7):638-46
pubmed: 23792630
PLoS Biol. 2023 Apr 24;21(4):e3002105
pubmed: 37093850
Biochim Biophys Acta. 1978 Oct 19;513(1):31-42
pubmed: 31173
Nat Commun. 2019 Sep 24;10(1):4333
pubmed: 31551417
N Engl J Med. 2020 Dec 31;383(27):2603-2615
pubmed: 33301246
Microsc Res Tech. 2012 May;75(5):691-7
pubmed: 22095650
Nano Lett. 2020 Feb 12;20(2):1117-1123
pubmed: 32003222
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016 May;8(3):465-78
pubmed: 26542891
RNA Biol. 2011 Jul-Aug;8(4):627-36
pubmed: 21654214
Curr Opin Biotechnol. 2022 Feb;73:329-336
pubmed: 34715546
ACS Nano. 2014 May 27;8(5):4559-70
pubmed: 24779637
FEBS Lett. 1977 Dec 15;84(2):323-6
pubmed: 598513
Biomater Sci. 2021 Jun 15;9(12):4289-4300
pubmed: 33586742
Eur J Pharm Biopharm. 2018 Aug;129:184-190
pubmed: 29859281
Nature. 1978 Feb 16;271(5646):672-4
pubmed: 625336
Nat Biotechnol. 2015 Aug;33(8):870-6
pubmed: 26192320
Colloids Surf B Biointerfaces. 2015 Dec 1;136:971-80
pubmed: 26562189
Molecules. 2012 Jan 20;17(1):1055-73
pubmed: 22267193
Mol Ther Nucleic Acids. 2019 Apr 15;15:1-11
pubmed: 30785039
Gene Ther. 2017 Mar;24(3):133-143
pubmed: 28094775
J Control Release. 2012 Feb 28;158(1):108-14
pubmed: 22056915
ACS Sens. 2020 Jul 24;5(7):1929-1936
pubmed: 32573202
J Virol. 1998 Dec;72(12):9645-55
pubmed: 9811698
Anal Biochem. 2005 Oct 1;345(1):55-65
pubmed: 16137634
Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18513-8
pubmed: 24167246
J Cell Biol. 2022 Feb 7;221(2):
pubmed: 34882187
Angew Chem Int Ed Engl. 2012 Aug 20;51(34):8529-33
pubmed: 22782619
Nat Commun. 2020 Apr 14;11(1):1809
pubmed: 32286269
Commun Biol. 2021 Aug 11;4(1):956
pubmed: 34381159
J Biol Chem. 2003 Nov 7;278(45):44826-31
pubmed: 12944394
J Biol Chem. 2008 Sep 5;283(36):24584-93
pubmed: 18591242
Biomol Concepts. 2017 Sep 26;8(3-4):131-141
pubmed: 28841567
Acc Chem Res. 2012 Jul 17;45(7):1153-62
pubmed: 22428908
Nat Rev Drug Discov. 2014 Oct;13(10):759-80
pubmed: 25233993
Pharmaceutics. 2023 Jan 03;15(1):
pubmed: 36678793
Pharmaceutics. 2020 Jun 07;12(6):
pubmed: 32517377
J Gene Med. 2005 May;7(5):657-63
pubmed: 15543529
Biomater Sci. 2019 Oct 1;7(10):3942-3960
pubmed: 31414096
Sci Adv. 2022 Jan 07;8(1):eabk2855
pubmed: 34985952
Nature. 2012 Jan 15;482(7385):414-8
pubmed: 22246324
J Control Release. 2022 Jul;347:521-532
pubmed: 35569584
Mol Pharm. 2009 May-Jun;6(3):763-71
pubmed: 19292453
Int J Mol Sci. 2020 Mar 24;21(6):
pubmed: 32213928
Cold Spring Harb Perspect Biol. 2014 Apr 01;6(4):a017012
pubmed: 24691962
J Cell Sci. 2018 Jul 6;131(13):
pubmed: 29980602
Nat Biotechnol. 2010 Feb;28(2):172-6
pubmed: 20081866
J Cell Sci. 2018 Nov 30;131(23):
pubmed: 30504135
N Engl J Med. 2021 Feb 4;384(5):403-416
pubmed: 33378609
Bioconjug Chem. 2010 Mar 17;21(3):537-43
pubmed: 20184308
Nat Rev Drug Discov. 2018 Apr;17(4):261-279
pubmed: 29326426
ACS Appl Mater Interfaces. 2022 Jul 6;14(26):30371-30384
pubmed: 35758331
Nat Commun. 2020 Feb 20;11(1):983
pubmed: 32080183
J Biol Chem. 2019 Feb 1;294(5):1706-1709
pubmed: 30710017
Nanoscale. 2016 Jul 14;8(26):13033-44
pubmed: 27314204
Lancet Oncol. 2022 Oct;23(10):e450-e458
pubmed: 36174631
J Control Release. 2010 Aug 3;145(3):182-95
pubmed: 20226220
Sci Adv. 2020 Nov 18;6(47):
pubmed: 33208369
Biomater Adv. 2022 Sep;140:213086
pubmed: 35988368
Nat Rev Methods Primers. 2021;1:
pubmed: 35663461
N Engl J Med. 2018 Jul 5;379(1):11-21
pubmed: 29972753
EMBO J. 2011 Aug 31;30(17):3481-500
pubmed: 21878991
Adv Healthc Mater. 2021 Aug;10(15):e2002022
pubmed: 33661555
Front Cell Infect Microbiol. 2013 Jul 30;3:37
pubmed: 23908972
Pharmaceutics. 2023 Apr 11;15(4):
pubmed: 37111695
Nano Lett. 2017 Sep 13;17(9):5711-5718
pubmed: 28836442
Mol Ther. 2019 Nov 6;27(11):1950-1962
pubmed: 31427168
Colloids Surf B Biointerfaces. 2013 May 1;105:284-93
pubmed: 23384691
Nat Commun. 2021 Jun 17;12(1):3721
pubmed: 34140497
J Biol Chem. 2009 Dec 4;284(49):33957-65
pubmed: 19833724
Viruses. 2011 Jun;3(6):920-40
pubmed: 21994762
Pharmaceutics. 2020 Jan 28;12(2):
pubmed: 32013049
Commun Biol. 2021 Feb 16;4(1):211
pubmed: 33594247
Langmuir. 2017 Jan 31;33(4):1051-1059
pubmed: 28059515
Biophys Chem. 2003 May 1;104(1):361-79
pubmed: 12834854
Biochim Biophys Acta Biomembr. 2017 Oct;1859(10):1749-1766
pubmed: 28655618
Nat Biotechnol. 2013 Jul;31(7):653-8
pubmed: 23792629
Sci Adv. 2023 Mar 10;9(10):eadg1036
pubmed: 36888708
Adv Sci (Weinh). 2023 May;10(13):e2300311
pubmed: 36905240