ArticleNature communications2025
Chemically modified CRISPR-Cas9 enables targeting of individual G-quadruplex and i-motif structures, revealing ligand-dependent transcriptional perturbation.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Dual recognition drives site-directed G-quadruplex stabilization: Oligonucleotide design in G4 ligand-oligonucleotide conjugates.Molecular therapy. Nucleic acids · 2026Article
- Polyamines are i-motif disruptors.Molecular therapy. Nucleic acids · 2026Article
- The G-force in the genome: Unknowns on the functional flairs of DNA G-quadruplexes.PLoS biology · 2026Article
- Azide-functionalized SpCas9 enables generation of site-selective and bioactive Cas9-siRNA conjugates.Chemical communications (Cambridge, England) · 2026Article
- Genome-wide mapping of DNA G-quadruplexes in Trypanosoma brucei chromatin reveals enrichment in coding regions and transcription start sites.Nucleic acids research · 2026Article
- Modulating G-quadruplexes for therapeutic intervention: Structural diversity, stability, and emerging nucleic-acid-based strategies.Molecular therapy. Nucleic acids · 2026Review
- Noble Metal Complexes and Non-Canonical Nucleic Acids: From G-Quadruplex Recognition to Emerging Functional Architectures.Biomolecules · 2026Review
- Precise discrimination of G-quadruplex conformation by chiral nanoassembly with photo-reversibility.Nature communications · 2026Article
- Endogenous promoter G-quadruplexes scaffold apurinic/apyrimidinic endonuclease (APE1) to drive gene expression.Nucleic acids research · 2026Article
- G-quadruplex stabilization via small molecules as a potential anti-cancer strategy.Cellular & molecular biology letters · 2026Review
- Telomeric repeat-containing RNA G-quadruplexes trigger ZBP1-mediated cell death.Nature communications · 2026Article
- Molecular recognition and effects of a benzothiazole derivative targeting the MYC G-quadruplex.Nucleic acids research · 2025Article
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17 authors.
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Abstract
The development of selective ligands to target DNA G-quadruplexes (G4s) and i-motifs (iMs) has revealed their relevance in transcriptional regulation. However, most of these ligands are unable to target individual G4s or iMs in the genome, limiting their scope. Herein, we describe an Approach to Target Exact Nucleic Acid alternative structures (ATENA) that relies on the chemical conjugation of established G4 and iM ligands to a catalytically inactive Cas9 protein (dCas9), enabling their individual targeting in living cells. ATENA demonstrates that the selective targeting of the G4 present in the oncogene c-MYC leads to the suppression of transcripts regulated exclusively by one of its promoters (P1). Conversely, targeting the c-MYC iMs on the opposite strand leads to the selective increase of P1-driven transcripts. ATENA reveals that G4-mediated transcriptional responses are highly ligand-specific, with different ligands eliciting markedly different effects at the same G4 site. We further demonstrate that the basal expression levels of the gene targeted can be used to predict the transcriptional impact associated with G4-stabilization. Our study provides a platform for investigating G4- and iM-biology with high precision, unveiling the therapeutic relevance of individual DNA structures with selectivity.
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