High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis

Suppression of gene expression due to aberrant promoter methylation contributes to organ fibrosis. Here, the authors couple a deactivated Cas9 to the TET3 catalytic domain to induce expression of four antifibrotic genes, and show that lentiviral-mediated delivery is effective in reducing kidney fibr...

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Main Authors: Xingbo Xu, Xiaoying Tan, Björn Tampe, Tim Wilhelmi, Melanie S. Hulshoff, Shoji Saito, Tobias Moser, Raghu Kalluri, Gerd Hasenfuss, Elisabeth M. Zeisberg, Michael Zeisberg
Format: Article
Language:English
Published: Nature Portfolio 2018-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-018-05766-5
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author Xingbo Xu
Xiaoying Tan
Björn Tampe
Tim Wilhelmi
Melanie S. Hulshoff
Shoji Saito
Tobias Moser
Raghu Kalluri
Gerd Hasenfuss
Elisabeth M. Zeisberg
Michael Zeisberg
author_facet Xingbo Xu
Xiaoying Tan
Björn Tampe
Tim Wilhelmi
Melanie S. Hulshoff
Shoji Saito
Tobias Moser
Raghu Kalluri
Gerd Hasenfuss
Elisabeth M. Zeisberg
Michael Zeisberg
author_sort Xingbo Xu
collection DOAJ
description Suppression of gene expression due to aberrant promoter methylation contributes to organ fibrosis. Here, the authors couple a deactivated Cas9 to the TET3 catalytic domain to induce expression of four antifibrotic genes, and show that lentiviral-mediated delivery is effective in reducing kidney fibrosis in mouse models.
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spelling doaj.art-8afce270d13543dc99f4fba3b97f9f222022-12-21T20:39:00ZengNature PortfolioNature Communications2041-17232018-08-019111510.1038/s41467-018-05766-5High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosisXingbo Xu0Xiaoying Tan1Björn Tampe2Tim Wilhelmi3Melanie S. Hulshoff4Shoji Saito5Tobias Moser6Raghu Kalluri7Gerd Hasenfuss8Elisabeth M. Zeisberg9Michael Zeisberg10Department of Cardiology and Pneumology, University Medical Center GöttingenGerman Center for Cardiovascular Research (DZHK) Partner SiteDepartment of Nephrology and Rheumatology, University Medical Center GöttingenDepartment of Cardiology and Pneumology, University Medical Center GöttingenDepartment of Cardiology and Pneumology, University Medical Center GöttingenDepartment of Nephrology and Rheumatology, University Medical Center GöttingenInstitute for Auditory Neuroscience & Inner Ear Lab, University Medical Center GöttingenDepartment of Cancer Biology, Metastasis Research Center, University of Texas, MD Anderson Cancer CenterDepartment of Cardiology and Pneumology, University Medical Center GöttingenDepartment of Cardiology and Pneumology, University Medical Center GöttingenGerman Center for Cardiovascular Research (DZHK) Partner SiteSuppression of gene expression due to aberrant promoter methylation contributes to organ fibrosis. Here, the authors couple a deactivated Cas9 to the TET3 catalytic domain to induce expression of four antifibrotic genes, and show that lentiviral-mediated delivery is effective in reducing kidney fibrosis in mouse models.https://doi.org/10.1038/s41467-018-05766-5
spellingShingle Xingbo Xu
Xiaoying Tan
Björn Tampe
Tim Wilhelmi
Melanie S. Hulshoff
Shoji Saito
Tobias Moser
Raghu Kalluri
Gerd Hasenfuss
Elisabeth M. Zeisberg
Michael Zeisberg
High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis
Nature Communications
title High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis
title_full High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis
title_fullStr High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis
title_full_unstemmed High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis
title_short High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis
title_sort high fidelity crispr cas9 based gene specific hydroxymethylation rescues gene expression and attenuates renal fibrosis
url https://doi.org/10.1038/s41467-018-05766-5
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