ArticleNature communications2018
High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 143 citations in OpenAlex.
- Effect of anti-fibrotic therapy on regression of myocardial fibrosis after TAVI: design and rationale of the Reduce-MFA DZHK25 trial.ESC heart failure · 2026Trial
- A practical toolbox for modelling fibrosis in vitro.Nature biomedical engineering · 2026Review
- From epigenetic mark detection to rational design of epigenetic editing strategies.Molecular therapy. Advances · 2026Review
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- Targeting pyroptosis in renal fibrosis: From molecular mechanisms to therapeutic horizons (Review).International journal of molecular medicine · 2026Review
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Epigenetic editing of marine medaka (Zoological research · 2026Article
- Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Epigenetic Suppression of RASAL1 by HDAC3 and Cofactor YY1 Promotes Fibroblast-Myofibroblast Transition and Renal Fibrosis.Research (Washington, D.C.) · 2026Article
- CRISPR-based Transcriptional Regulation: Technologies, Applications, and Future Directions.DNA · 2025Article
- CRISPR Technology and Its Emerging Applications.Genomics, proteomics & bioinformatics · 2025Review
- Epigenome Engineering Using dCas Systems for Biomedical Applications and Biotechnology: Current Achievements, Opportunities and Challenges.International journal of molecular sciences · 2025Review
- The Role of Cardiac Fibroblast Heterogeneity in Myocardial Fibrosis and Its Novel Therapeutic Potential.International journal of molecular sciences · 2025Review
- Inhibition of epigenetic regulator UHRF1 attenuates renal fibrosis and retains transcription factor Krüppel-like factor 15 expression.Cell death discovery · 2025Article
- Advancements in CRISPR/Cas systems for disease treatment.Acta pharmaceutica Sinica. B · 2025Review
- DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities.Clinical epigenetics · 2025Review
- Integration of DNA Methylome and Transcriptome Analysis to Identify Novel Epigenetic Targets in the Acute Kidney Injury-Chronic Kidney Disease Transition.Biomolecules · 2025Article
- The Impact of Klotho in Cancer: From Development and Progression to Therapeutic Potential.Genes · 2025Review
- Gene Therapy Techniques and Delivery Methods (Review).Sovremennye tekhnologii v meditsine · 2025Review
- New approaches to acute kidney injury.Clinical kidney journal · 2024Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While suppression of specific genes through aberrant promoter methylation contributes to different diseases including organ fibrosis, gene-specific reactivation technology is not yet available for therapy. TET enzymes catalyze hydroxymethylation of methylated DNA, reactivating gene expression. We here report generation of a high-fidelity CRISPR/Cas9-based gene-specific dioxygenase by fusing an endonuclease deactivated high-fidelity Cas9 (dHFCas9) to TET3 catalytic domain (TET3CD), targeted to specific genes by guiding RNAs (sgRNA). We demonstrate use of this technology in four different anti-fibrotic genes in different cell types in vitro, among them RASAL1 and Klotho, both hypermethylated in kidney fibrosis. Furthermore, in vivo lentiviral delivery of the Rasal1-targeted fusion protein to interstitial cells and of the Klotho-targeted fusion protein to tubular epithelial cells each results in specific gene reactivation and attenuation of fibrosis, providing gene-specific demethylating technology in a disease model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.