Your browser doesn't support javascript.
loading
An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.
Yan, Ruorong; Cigliola, Valentina; Oonk, Kelsey A; Petrover, Zachary; DeLuca, Sophia; Wolfson, David W; Vekstein, Andrew; Mendiola, Michelle A; Devlin, Garth; Bishawi, Muath; Gemberling, Matthew P; Sinha, Tanvi; Sargent, Michelle A; York, Allen J; Shakked, Avraham; DeBenedittis, Paige; Wendell, David C; Ou, Jianhong; Kang, Junsu; Goldman, Joseph A; Baht, Gurpreet S; Karra, Ravi; Williams, Adam R; Bowles, Dawn E; Asokan, Aravind; Tzahor, Eldad; Gersbach, Charles A; Molkentin, Jeffery D; Bursac, Nenad; Black, Brian L; Poss, Kenneth D.
Afiliação
  • Yan R; Duke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA.
  • Cigliola V; Duke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA.
  • Oonk KA; Duke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA.
  • Petrover Z; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • DeLuca S; Department of Cell Biology, Duke University Medical School, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA.
  • Wolfson DW; Duke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA.
  • Vekstein A; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Mendiola MA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Devlin G; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Bishawi M; Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Gemberling MP; Department of Biomedical Engineering, Duke University, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA.
  • Sinha T; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
  • Sargent MA; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
  • York AJ; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
  • Shakked A; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • DeBenedittis P; Department of Medicine, Duke University Medical Center, Durham, NC, USA.
  • Wendell DC; Duke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, Durham, NC, USA.
  • Ou J; Duke Regeneration Center, Duke University, Durham, NC, USA.
  • Kang J; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
  • Goldman JA; Department of Biological Chemistry and Pharmacology, Ohio State University, Columbus, OH, USA.
  • Baht GS; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Karra R; Department of Medicine, Duke University Medical Center, Durham, NC, USA.
  • Williams AR; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Bowles DE; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Asokan A; Duke Regeneration Center, Duke University, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA.
  • Tzahor E; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Gersbach CA; Duke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA; Center for Adva
  • Molkentin JD; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
  • Bursac N; Department of Biomedical Engineering, Duke University, Durham, NC, USA.
  • Black BL; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
  • Poss KD; Duke Regeneration Center, Duke University, Durham, NC, USA; Department of Cell Biology, Duke University Medical School, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA. Electronic address: ken.poss@duke.edu.
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.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regeneração / Terapia Genética / Elementos Facilitadores Genéticos / Miócitos Cardíacos / Coração / Infarto do Miocárdio Limite: Animals Idioma: En Revista: Cell Stem Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regeneração / Terapia Genética / Elementos Facilitadores Genéticos / Miócitos Cardíacos / Coração / Infarto do Miocárdio Limite: Animals Idioma: En Revista: Cell Stem Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos