ArticleACS synthetic biology2022
Bioorthogonal Chemical Epigenetic Modifiers Enable Dose-Dependent CRISPR Targeted Gene Activation in Mammalian Cells.
Article in ACS synthetic biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- From epigenetic mark detection to rational design of epigenetic editing strategies.Molecular therapy. Advances · 2026Review
- A First-in-Class Chemical-Induced Proximity System Achieves Dose-Dependent Control of Tumor Protein P53 Gene Activation in Preclinical Models of Gastric Cancer.ACS pharmacology & translational science · 2025Article
- Dynamic activation of rAAV transgene expression by a small molecule that recruits endogenous transcriptional machinery.Nucleic acids research · 2025Article
- Induced proximity labeling and editing for epigenetic research.Cell chemical biology · 2024Review
- Fine-Tuning the Epigenetic Landscape: Chemical Modulation of Epigenome Editors.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Chemical Epigenetic Regulation of Adeno-Associated Virus Delivered Transgenes.Human gene therapy · 2023Article
- Characterization of Hepatoma-Derived Growth Factor-Related Protein 2 Interactions with Heterochromatin.Cells · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
CRISPR-Cas9 systems have been developed to regulate gene expression by using either fusions to epigenetic regulators or, more recently, through the use of chemically mediated strategies. These approaches have armed researchers with new tools to examine the function of proteins by intricately controlling expression levels of specific genes. Here we present a CRISPR-based chemical approach that uses a new chemical epigenetic modifier (CEM) to hone to a gene targeted with a catalytically inactive Cas9 (dCas9) bridged to an FK506-binding protein (FKBP) in mammalian cells. One arm of the bifunctional CEM recruits BRD4 to the target site, and the other arm is composed of a bumped ligand that binds to a mutant FKBP with a compensatory hole at F36V. This bump-and-hole strategy allows for activation of target genes in a dose-dependent and reversible fashion with increased specificity and high efficacy, providing a new synthetic biology approach to answer important mechanistic questions in the future.
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Registered trials
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