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

Publication ,  Journal Article
Yan, R; Cigliola, V; Oonk, KA; Petrover, Z; DeLuca, S; Wolfson, DW; Vekstein, A; Mendiola, MA; Devlin, G; Bishawi, M; Gemberling, MP; Sinha, T ...
Published in: Cell stem cell
January 2023

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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Published In

Cell stem cell

DOI

EISSN

1875-9777

ISSN

1934-5909

Publication Date

January 2023

Volume

30

Issue

1

Start / End Page

96 / 111.e6

Related Subject Headings

  • Zebrafish
  • Regeneration
  • Myocytes, Cardiac
  • Myocardial Infarction
  • Mice
  • Heart
  • Genetic Therapy
  • Enhancer Elements, Genetic
  • Developmental Biology
  • Cell Proliferation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yan, R., Cigliola, V., Oonk, K. A., Petrover, Z., DeLuca, S., Wolfson, D. W., … Poss, K. D. (2023). An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair. Cell Stem Cell, 30(1), 96-111.e6. https://doi.org/10.1016/j.stem.2022.11.012
Yan, Ruorong, Valentina Cigliola, Kelsey A. Oonk, Zachary Petrover, Sophia DeLuca, David W. Wolfson, Andrew Vekstein, et al. “An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.Cell Stem Cell 30, no. 1 (January 2023): 96-111.e6. https://doi.org/10.1016/j.stem.2022.11.012.
Yan R, Cigliola V, Oonk KA, Petrover Z, DeLuca S, Wolfson DW, et al. An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair. Cell stem cell. 2023 Jan;30(1):96-111.e6.
Yan, Ruorong, et al. “An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.Cell Stem Cell, vol. 30, no. 1, Jan. 2023, pp. 96-111.e6. Epmc, doi:10.1016/j.stem.2022.11.012.
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. An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair. Cell stem cell. 2023 Jan;30(1):96-111.e6.
Journal cover image

Published In

Cell stem cell

DOI

EISSN

1875-9777

ISSN

1934-5909

Publication Date

January 2023

Volume

30

Issue

1

Start / End Page

96 / 111.e6

Related Subject Headings

  • Zebrafish
  • Regeneration
  • Myocytes, Cardiac
  • Myocardial Infarction
  • Mice
  • Heart
  • Genetic Therapy
  • Enhancer Elements, Genetic
  • Developmental Biology
  • Cell Proliferation