ArticleNature communications2024
Specific multivalent molecules boost CRISPR-mediated transcriptional activation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Injectable Supramolecular Hydrogel Encapsulating CRISPR-Engineered MSCs Drives Synergistic Neuroprotection and Functional Recovery After Traumatic Brain Injury.Advanced healthcare materials · 2026Article
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- CRISPR/Cas‑based epigenome editing for osteogenic lineage commitment.Cell and tissue research · 2026Review
- Spatially concentrated adenine base editors efficiently correct PLP1 mutations in oligodendrocytes.Nucleic acids research · 2026Article
- Repurposing nuclear receptors for ligand-responsive liquid condensate formation and gene regulation.Nature communications · 2026Article
- Harnessing the potential of gene editing technology for CAR-T cell therapy of solid tumors.Inflammation and regeneration · 2025Review
- Metabolite-responsive scaffold RNAs for dynamic CRISPR transcriptional regulation.Nucleic acids research · 2025Article
- New power in cancer immunotherapy: the rise of chimeric antigen receptor macrophage (CAR-M).Journal of translational medicine · 2025Review
- Programmable genome engineering and gene modifications for plant biodesign.Plant communications · 2025Review
- Precision sniper for solid tumors: CAR-NK cell therapy.Cancer immunology, immunotherapy : CII · 2025Review
- Epigenome Engineering Using dCas Systems for Biomedical Applications and Biotechnology: Current Achievements, Opportunities and Challenges.International journal of molecular sciences · 2025Review
- Dynamic properties of transcriptional condensates modulate CRISPRa-mediated gene activation.Nature communications · 2025Article
- A sensitive red/far-red photoswitch for controllable gene therapy in mouse models of metabolic diseases.Nature communications · 2024Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CRISPR/Cas-based transcriptional activators can be enhanced by intrinsically disordered regions (IDRs). However, the underlying mechanisms are still debatable. Here, we examine 12 well-known IDRs by fusing them to the dCas9-VP64 activator, of which only seven can augment activation, albeit independently of their phase separation capabilities. Moreover, modular domains (MDs), another class of multivalent molecules, though ineffective in enhancing dCas9-VP64 activity on their own, show substantial enhancement in transcriptional activation when combined with dCas9-VP64-IDR. By varying the number of gRNA binding sites and fusing dCas9-VP64 with different IDRs/MDs, we uncover that optimal, rather than maximal, cis-trans cooperativity enables the most robust activation. Finally, targeting promoter-enhancer pairs yields synergistic effects, which can be further amplified via enhancing chromatin interactions. Overall, our study develops a versatile platform for efficient gene activation and sheds important insights into CRIPSR-based transcriptional activators enhanced with multivalent molecules.
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