ArticleNature communications2024
Specificity, synergy, and mechanisms of splice-modifying drugs.
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 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- Real-world 12-month outcomes of Risdiplam in spinal muscular atrophy types 2 and 3: A Brazilian cohort.Clinics (Sao Paulo, Brazil) · 2026Article
- The U1 snRNP protein U1C and Helix H of U1 snRNA are critical for small molecule splicing modulator function.Nature communications · 2026Article
- Specificity and exon target space of splicing modifying compounds.Nature communications · 2026Article
- Inference of fitness landscapes with heterogeneous patterns of epistasis across sites.bioRxiv : the preprint server for biology · 2026Article
- Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 2026Article
- Predicting human mRNA isoform levels from site-specific splicing kineticsbioRxiv : the preprint server for biology · 2026Article
- Tunable gene control via RNA splicing with a clinically approved small molecule.Nature communications · 2026Article
- An approach for the systematic profiling of drug-induced remodeling of RNA-RBP (RNA-binding protein) interactions.RSC advances · 2026Article
- RNA functional modulation by Mitoxantrone via RNA structural ensemble repartitioning.Nature communications · 2026Article
- Systematic identification of variant-specific RNA structure-small molecule interactions exemplified by RNA G-quadruplexes.Nature communications · 2026Article
- RNA localization to nuclear speckles follows splicing logic.Nucleic acids research · 2026Article
- Chemically-inducible CRISPR/Cas9 circuits for ultra-high dynamic range gene perturbation.Nature communications · 2025Article
- A Chemically Induced CRISPR/dCas13Journal of medicinal chemistry · 2025Article
- All-at-once RNA folding with 3D motif prediction framed by evolutionary information.Nature methods · 2025Article
- Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4.Nature structural & molecular biology · 2025Article
- Review
- Learning sequence-function relationships with scalable, interpretable Gaussian processes.bioRxiv : the preprint server for biology · 2025Article
- The drug-elicitable alternative splicing module for tunable vector expression in the heart.Nature cardiovascular research · 2025Article
- Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Drugs that target pre-mRNA splicing hold great therapeutic potential, but the quantitative understanding of how these drugs work is limited. Here we introduce mechanistically interpretable quantitative models for the sequence-specific and concentration-dependent behavior of splice-modifying drugs. Using massively parallel splicing assays, RNA-seq experiments, and precision dose-response curves, we obtain quantitative models for two small-molecule drugs, risdiplam and branaplam, developed for treating spinal muscular atrophy. The results quantitatively characterize the specificities of risdiplam and branaplam for 5' splice site sequences, suggest that branaplam recognizes 5' splice sites via two distinct interaction modes, and contradict the prevailing two-site hypothesis for risdiplam activity at SMN2 exon 7. The results also show that anomalous single-drug cooperativity, as well as multi-drug synergy, are widespread among small-molecule drugs and antisense-oligonucleotide drugs that promote exon inclusion. Our quantitative models thus clarify the mechanisms of existing treatments and provide a basis for the rational development of new therapies.
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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.