An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.
Cell Stem Cell
; 30(1): 96-111.e6, 2023 01 05.
Article
em En
| MEDLINE
| ID: mdl-36516837
ABSTRACT
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Terapia Genética
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Elementos Facilitadores Genéticos
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Miócitos Cardíacos
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Coração
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Infarto do Miocárdio
Limite:
Animals
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos