An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Yan, R; Cigliola, V; Oonk, KA; Petrover, Z; DeLuca, S; Wolfson, DW; Vekstein, A; Mendiola, MA; Devlin, G; Bishawi, M; Gemberling, MP; Sinha, T; Sargent, MA; York, AJ; Shakked, A; DeBenedittis, P; Wendell, DC; Ou, J; Kang, J; Goldman, JA; Baht, GS; Karra, R; Williams, AR; Bowles, DE; Asokan, A; Tzahor, E; Gersbach, CA; Molkentin, JD; Bursac, N; Black, BL; Poss, KD

Published Date

  • January 5, 2023

Published In

Volume / Issue

  • 30 / 1

Start / End Page

  • 96 - 111.e6

PubMed ID

  • 36516837

Pubmed Central ID

  • PMC9830588

Electronic International Standard Serial Number (EISSN)

  • 1875-9777

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2022.11.012


  • eng

Conference Location

  • United States