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
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regeneración
/
Terapia Genética
/
Elementos de Facilitación Genéticos
/
Miocitos Cardíacos
/
Corazón
/
Infarto del Miocardio
Límite:
Animals
Idioma:
En
Revista:
Cell Stem Cell
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos