ArticleNature methods2023
Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control.
Article in Nature methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 38 citations in OpenAlex.
- From epigenetic mark detection to rational design of epigenetic editing strategies.Molecular therapy. Advances · 2026Review
- TIGRa: An ultra-compact programmable activator enabling multiplexed and efficient gene regulation.Cell stem cell · 2026Article
- CRISPR-Cas-based activation of PPARGC1A boosts endogenous mitochondria and enhances cardiac function after myocardial infarction.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Combinatorial and Inducible CRISPRa/i Enables Canalized hiPSC Forward Programming and Iterative RefinementbioRxiv : the preprint server for biology · 2026Article
- Next generation technologies for CRISPR-based epigenome and transcriptional modulation.Current opinion in biomedical engineering · 2026Article
- Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026Article
- CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.Molecular therapy. Nucleic acids · 2026Review
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Efficient clustered, regularly interspaced short palindromic repeats-based gene activation using combinatorial human transcription activation domains.Protein & cell · 2026Article
- Article
- A compact and inducible dCas12f-based CRISPRa platform for programmable in vivo gene activation.Nature communications · 2026Article
- CRISPR-based Transcriptional Regulation: Technologies, Applications, and Future Directions.DNA · 2025Article
- Vector-free intra-airway in vivo epigenetic editing.Trends in biotechnology · 2025Article
- Development of compact transcriptional effectors using high-throughput measurements in diverse contexts.Nature biotechnology · 2025Article
- Cytotoxicity of activator expression in CRISPR-based transcriptional activation systems.Nature communications · 2025Article
- Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025Review
- Dissecting the epigenetic regulation of the fetal hemoglobin genes to unravel a novel therapeutic approach for β-hemoglobinopathies.Nucleic acids research · 2025Article
- Recent advances in therapeutic gene-editing technologies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Efficient DNA- and virus-free engineering of cellular transcriptomic states using dCas9 ribonucleoprotein (dRNP) complexes.Nucleic acids research · 2025Article
- 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
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Engineered transactivation domains (TADs) combined with programmable DNA binding platforms have revolutionized synthetic transcriptional control. Despite recent progress in programmable CRISPR-Cas-based transactivation (CRISPRa) technologies, the TADs used in these systems often contain poorly tolerated elements and/or are prohibitively large for many applications. Here, we defined and optimized minimal TADs built from human mechanosensitive transcription factors. We used these components to construct potent and compact multipartite transactivation modules (MSN, NMS and eN3x9) and to build the CRISPR-dCas9 recruited enhanced activation module (CRISPR-DREAM) platform. We found that CRISPR-DREAM was specific and robust across mammalian cell types, and efficiently stimulated transcription from diverse regulatory loci. We also showed that MSN and NMS were portable across Type I, II and V CRISPR systems, transcription activator-like effectors and zinc finger proteins. Further, as proofs of concept, we used dCas9-NMS to efficiently reprogram human fibroblasts into induced pluripotent stem cells and demonstrated that mechanosensitive transcription factor TADs are efficacious and well tolerated in therapeutically important primary human cell types. Finally, we leveraged the compact and potent features of these engineered TADs to build dual and all-in-one CRISPRa AAV systems. Altogether, these compact human TADs, fusion modules and delivery architectures should be valuable for synthetic transcriptional control in biomedical applications.
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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.