ArticleTranslational neurodegeneration2022
CRISPR/dCas9-Dnmt3a-mediated targeted DNA methylation of APP rescues brain pathology in a mouse model of Alzheimer's disease.
Article in Translational neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 60 citations in OpenAlex.
- An Overview of Programmable Epigenetic Editing Based on CRISPR Tools for Gene Expression Regulation.Methods in molecular biology (Clifton, N.J.) · 2027Review
- The role of DNA methylation in the regulation of HLA expression.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2026Review
- Silencing of humanJournal of Huntington's disease · 2026Article
- Therapeutic Gene Editing of APOE4 in Sporadic Alzheimer's Disease via Prime Editor 7.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial-Epigenetic Crosstalk in Autism Spectrum Disorder: Linking Cellular Stress to Synaptic Dysfunction and Treatment Resistance.Molecular neurobiology · 2026Review
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- Recent Developments in Lipid Nanoparticle-Mediated Delivery of Biotherapeutics and Gene Therapy Across the Blood-Brain Barrier.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- CRISPR Interference to Inhibit Oncogenes for Cancer Therapy.International journal of molecular sciences · 2026Review
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- 5-Hydroxymethylcytosine profiles in circulating cell-free DNA serve as potential biomarkers for diagnosis and classification of adenomyosis.EBioMedicine · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Aberrant neural stem cell quiescence is the gateway to autism development linked to Arid1b.Molecular psychiatry · 2026Article
- 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
- Targeted methylation of cg24067911 suppresses colorectal cancer metastasis through BCL6-ATXN1-CDH1 axis.Oncogene · 2026Article
- Review
- Systematic enhancer mapping and functional analysis in zebrafish with optimized CRISPR interference.Nucleic acids research · 2025Article
- Harnessing the potential of gene editing technology for CAR-T cell therapy of solid tumors.Inflammation and regeneration · 2025Review
- DNA methylation as a new frontier in treating fear-related disorders: A need for careful evaluation.World journal of psychiatry · 2025Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant DNA methylation patterns have been observed in neurodegenerative diseases, including Alzheimer's disease (AD), and dynamic changes in DNA methylation are closely associated with the onset and progression of these diseases. Particularly, hypomethylation of the amyloid precursor protein gene (APP) has been reported in patients with AD.
methodsIn this study, we used catalytically inactivated Cas9 (dCas9) fused with Dnmt3a for targeted DNA methylation of APP, and showed that the CRISPR/dCas9-Dnmt3a-mediated DNA methylation system could efficiently induce targeted DNA methylation of APP both in vivo and in vitro.
resultsWe hypothesized that the targeted methylation of the APP promoter might rescue AD-related neuronal cell death by reducing APP mRNA expression. The cultured APP-KI mouse primary neurons exhibited an altered DNA-methylation pattern on the APP promoter after dCas9-Dnmt3a treatment. Likewise, the APP mRNA level was significantly reduced in the dCas9-Dnmt3a-treated wild-type and APP-KI mouse primary neurons. We also observed decreased amyloid-beta (Aβ) peptide level and Aβ42/40 ratio in the dCas9-Dnmt3a-treated APP-KI mouse neurons compared to the control APP-KI mouse neurons. In addition, neuronal cell death was significantly decreased in the dCas9-Dnmt3a-treated APP-KI mouse neurons. Furthermore, the in vivo methylation of APP in the brain via dCas9-Dnmt3a treatment altered Aβ plaques and attenuated cognitive and behavioral impairments in the APP-KI mouse model.
conclusionsThese results suggest that the targeted methylation of APP via dCas9-Dnmt3a treatment can be a potential therapeutic strategy for AD.
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