ArticleInternational journal of molecular sciences2020
Engineering of Effector Domains for Targeted DNA Methylation with Reduced Off-Target Effects.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 63 citations in OpenAlex.
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Comprehensive profiling of CRISPR/dCas9 epigenome editors indicates a complex link between on and off target effects.Genome biology · 2026Article
- Gut microbes-spinal connection is required for itch sensation.Gut microbes · 2025Article
- All-in-one vectors for epigenetic CRISPR inhibition ofMolecular therapy. Methods & clinical development · 2025Article
- SERBP1-PCIF1 complex-controlled m6Am modification in glutamatergic neurons of the primary somatosensory cortex is required for neuropathic pain in mice.Nature communications · 2025Article
- Epigenome Engineering Using dCas Systems for Biomedical Applications and Biotechnology: Current Achievements, Opportunities and Challenges.International journal of molecular sciences · 2025Review
- Characterization of Rationally Designed CRISPR/Cas9-Based DNA Methyltransferases with Distinct Methyltransferase and Gene Silencing Activities in Human Cell Lines and Primary Human T Cells.ACS synthetic biology · 2025Article
- Ultrasound Control of Genomic Regulatory Toolboxes for Cancer Immunotherapy.Nature communications · 2024Article
- Allele-specific DNA demethylation editing leads to stable upregulation of allele-specific gene expression.iScience · 2024Article
- Tailoring a CRISPR/Cas-based Epigenome Editor for Programmable Chromatin Acylation and Decreased Cytotoxicity.bioRxiv : the preprint server for biology · 2024Article
- Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor.Science (New York, N.Y.) · 2024Article
- CRISPR technologies for genome, epigenome and transcriptome editing.Nature reviews. Molecular cell biology · 2024Review
- Comparative ethical evaluation of epigenome editing and genome editing in medicine: first steps and future directions.Journal of medical ethics · 2024Article
- Review
- Article
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Targeting oncogenic TERT promoter variants by allele-specific epigenome editing.Clinical epigenetics · 2023Article
- Development of super-specific epigenome editing by targeted allele-specific DNA methylation.Epigenetics & chromatin · 2023Article
- The Design and Application of DNA-Editing Enzymes as Base Editors.Annual review of biochemistry · 2023Review
- Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance.Biomedicines · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Epigenome editing is a promising technology, potentially allowing the stable reprogramming of gene expression profiles without alteration of the DNA sequence. Targeted DNA methylation has been successfully documented by many groups for silencing selected genes, but recent publications have raised concerns regarding its specificity. In the current work, we developed new EpiEditors for programmable DNA methylation in cells with a high efficiency and improved specificity. First, we demonstrated that the catalytically deactivated Cas9 protein (dCas9)-SunTag scaffold, which has been used earlier for signal amplification, can be combined with the DNMT3A-DNMT3L single-chain effector domain, allowing for a strong methylation at the target genomic locus. We demonstrated that off-target activity of this system is mainly due to untargeted freely diffusing DNMT3A-DNMT3L subunits. Therefore, we generated several DNMT3A-DNMT3L variants containing mutations in the DNMT3A part, which reduced their endogenous DNA binding. We analyzed the genome-wide DNA methylation of selected variants and confirmed a striking reduction of untargeted methylation, most pronounced for the R887E mutant. For all potential applications of targeted DNA methylation, the efficiency and specificity of the treatment are the key factors. By developing highly active targeted methylation systems with strongly improved specificity, our work contributes to future applications of this approach.
Indexed as
Identifiers
What OpenQuestion holds
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.