An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.
YAP
cardiomyocyte proliferation
enhancers
gene therapy
heart regeneration
mouse
pig
tissue regeneration
zebrafish
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
05 01 2023
05 01 2023
Historique:
received:
27
02
2022
revised:
06
10
2022
accepted:
15
11
2022
pmc-release:
05
01
2024
pubmed:
15
12
2022
medline:
11
1
2023
entrez:
14
12
2022
Statut:
ppublish
Résumé
The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) isolated from zebrafish can direct targeted, injury-associated gene expression from viral DNA vectors delivered systemically in small and large adult mammalian species. When employed in combination with CRISPR-based epigenome editing tools in mice, zebrafish TREEs stimulated or repressed the expression of endogenous genes after ischemic myocardial infarction. Intravenously delivered recombinant AAV vectors designed with a TREE to direct a constitutively active YAP factor boosted indicators of cardiac regeneration in mice and improved the function of the injured heart. Our findings establish the application of contextual enhancer elements as a potential therapeutic platform for spatiotemporally controlled tissue regeneration in mammals.
Identifiants
pubmed: 36516837
pii: S1934-5909(22)00459-3
doi: 10.1016/j.stem.2022.11.012
pmc: PMC9830588
mid: NIHMS1858391
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
96-111.e6Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL146366
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG012053
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL126524
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI146356
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL150713
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119621
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151522
Pays : United States
Organisme : NHGRI NIH HHS
ID : RM1 HG011123
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG028716
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136182
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL157277
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 17SDG33660922
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL164013
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL134764
Pays : United States
Organisme : NIDA NIH HHS
ID : R33 DA041878
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG067245
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 16SDG30020001
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL162460
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests R.Y., J.K., J.A.G., V.C., and K.D.P. are listed as inventors on a patent application filed by Duke University on methods for enhancing tissue regeneration. C.A.G. is an inventor on patents and patent applications related to epigenome editing, is a co-founder/advisor of Tune Therapeutics and Locus Biosciences, and is an advisor to Sarepta Therapeutics.
Références
Nat Genet. 2017 Sep;49(9):1346-1353
pubmed: 28783163
Nat Biotechnol. 2015 May;33(5):510-7
pubmed: 25849900
Methods Mol Biol. 2021;2189:65-69
pubmed: 33180293
Genome Res. 2018 Dec;28(12):1852-1866
pubmed: 30459214
Science. 2021 Sep 24;373(6562):1537-1540
pubmed: 34554778
Mol Ther Methods Clin Dev. 2020 Sep 01;19:120-138
pubmed: 33209958
Nature. 2017 Oct 12;550(7675):260-264
pubmed: 28976966
Dev Cell. 2017 Feb 27;40(4):392-404.e5
pubmed: 28245924
Sci Signal. 2015 May 05;8(375):ra41
pubmed: 25943351
Development. 2013 Dec;140(23):4683-90
pubmed: 24255096
Cell. 2018 Mar 22;173(1):104-116.e12
pubmed: 29502971
J Hand Surg Br. 1995 Feb;20(1):63-71
pubmed: 7759939
Science. 2002 Dec 13;298(5601):2188-90
pubmed: 12481136
Nat Med. 2019 Mar;25(3):427-432
pubmed: 30778238
Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13839-44
pubmed: 23918388
Bone. 2015 Aug;77:31-41
pubmed: 25886903
Methods Mol Biol. 2021;2158:3-21
pubmed: 32857361
Elife. 2016 Feb 03;5:
pubmed: 26840050
Development. 2011 Aug;138(16):3421-30
pubmed: 21752928
Dev Dyn. 2021 Sep;250(9):1330-1339
pubmed: 33064344
Cardiovasc Res. 2008 Apr 1;78(1):18-25
pubmed: 18079102
Expert Opin Biol Ther. 2022 Sep;22(9):1117-1135
pubmed: 35428407
Circ Res. 2014 Jul 18;115(3):354-63
pubmed: 24833660
Development. 2022 Feb 15;149(4):
pubmed: 35179181
Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18455-18465
pubmed: 31451669
Development. 2020 Jul 30;147(14):
pubmed: 32665240
Nature. 2020 Nov;587(7835):613-618
pubmed: 33029008
Nat Methods. 2021 Aug;18(8):965-974
pubmed: 34341582
Science. 2011 Apr 22;332(6028):458-61
pubmed: 21512031
Dev Cell. 2017 May 22;41(4):382-391.e5
pubmed: 28535373
Nat Rev Genet. 2020 Apr;21(4):255-272
pubmed: 32042148
Science. 2011 Feb 25;331(6020):1078-80
pubmed: 21350179
Theranostics. 2019 Aug 14;9(21):6099-6111
pubmed: 31534539
Hum Gene Ther. 2011 Sep;22(9):1143-53
pubmed: 21476867
Circulation. 2021 Jun;143(22):2143-2154
pubmed: 33820424
Nat Methods. 2015 Dec;12(12):1143-9
pubmed: 26501517
Nature. 2017 Jul 13;547(7662):179-184
pubmed: 28581497
Nature. 2016 Apr 14;532(7598):201-6
pubmed: 27049946
Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1754-60
pubmed: 16699071
Elife. 2020 Jun 03;9:
pubmed: 32490812
Annu Rev Med. 2022 Sep 14;:
pubmed: 36103998
Nat Commun. 2021 Oct 29;12(1):6239
pubmed: 34716331
Science. 2020 Sep 4;369(6508):
pubmed: 32883834
Circulation. 2021 Apr 6;143(14):1343-1358
pubmed: 33478245
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Gene Ther. 2008 Nov;15(22):1489-99
pubmed: 18563184
Mol Ther. 2006 Jul;14(1):45-53
pubmed: 16713360
Nat Rev Genet. 2020 Sep;21(9):511-525
pubmed: 32504079
Nat Rev Drug Discov. 2021 Mar;20(3):173-174
pubmed: 33495615
Mech Dev. 2003 Sep;120(9):1021-32
pubmed: 14550531
Cell. 2013 Jul 18;154(2):442-51
pubmed: 23849981
Methods Mol Biol. 2016;1382:81-91
pubmed: 26611580
Nature. 2010 Mar 25;464(7288):601-5
pubmed: 20336144
Front Cardiovasc Med. 2022 Feb 10;9:833335
pubmed: 35224061
Science. 2019 Apr 12;364(6436):184-188
pubmed: 30846611
Cell. 2014 Apr 24;157(3):565-79
pubmed: 24766806
Science. 2016 Sep 9;353(6304):1123-9
pubmed: 27609886
Dev Cell. 2019 Mar 25;48(6):765-779.e7
pubmed: 30773489
Am J Physiol. 1996 Nov;271(5 Pt 2):H2183-9
pubmed: 8945939
Nat Cell Biol. 2015 May;17(5):627-38
pubmed: 25848746
J Pediatr Surg. 1974 Dec;9(6):853-58
pubmed: 4473530
Nature. 2012 Dec 20;492(7429):376-81
pubmed: 23222520
J Biol Chem. 2005 Sep 23;280(38):32602-8
pubmed: 16043490
Nat Cell Biol. 2020 Nov;22(11):1346-1356
pubmed: 33046882
J Hand Surg Br. 1993 Apr;18(2):230-3
pubmed: 8501382
Dev Cell. 2011 Mar 15;20(3):397-404
pubmed: 21397850
Dev Cell. 2014 Jul 28;30(2):137-50
pubmed: 25043473
Neurobiol Dis. 2021 Feb;149:105235
pubmed: 33383186
Genome Biol. 2020 Feb 27;21(1):52
pubmed: 32106888
J Orthop Res. 2014 Apr;32(4):581-6
pubmed: 24347536
Science. 2019 Mar 15;363(6432):
pubmed: 30872491
Cell. 2017 Dec 14;171(7):1495-1507.e15
pubmed: 29224783