ArticleCell2012
Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression.
Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
161 citing papers in PubMed, 275 citations in OpenAlex.
- Integrated Assessment of the Clinical Performance of GalNAcNucleic acid therapeutics · 2019Trial
- Argonaute-mediated RNA editing selectively repairs point mutations.Nucleic acids research · 2026Article
- Effects of RNAi of Ribophorin 1, Eukaryotic translation initiation factor 2 beta and Peptidylprolyl isomerase A inBiochemistry & molecular biology journal · 2026Article
- RNA Therapeutics in Heart Failure.Journal of cardiovascular translational research · 2025Review
- Endogenous Ribonucleases: Therapeutic Targeting of the Transcriptome Through Oligonucleotide-Triggered RNA Inactivation.Biomolecules · 2025Review
- Pharmaceutical perspectives on oligonucleotide therapeutics and delivery systems.Pharmacological reviews · 2025Review
- Nucleic Acid Conjugates: Unlocking Therapeutic Potential.ACS bio & med chem Au · 2025Review
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Insights into RNA-mediated pathology in new mouse models of Huntington's disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Advancements in surgical treatments for Huntington disease: From pallidotomy to experimental therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Sequencing-guided design of genetically encoded small RNAs targeting CAG repeats for selective inhibition of mutantMolecular therapy. Nucleic acids · 2024Article
- RNAi-based drug design: considerations and future directions.Nature reviews. Drug discovery · 2024Review
- Review
- AAV-Mediated CAG-Targeting Selectively Reduces Polyglutamine-Expanded Protein and Attenuates Disease Phenotypes in a Spinocerebellar Ataxia Mouse Model.International journal of molecular sciences · 2024Article
- Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.Cell chemical biology · 2024Review
- Review
- XRN2 suppresses aberrant entry of tRNA trailers into argonaute in humans and Arabidopsis.PLoS genetics · 2023Article
- Evolutionarily Conserved Role of Thioredoxin Systems in Determining Longevity.Antioxidants (Basel, Switzerland) · 2023Review
- Structural Modifications of siRNA Improve Its Performance In Vivo.International journal of molecular sciences · 2023Review
- Recent approaches on Huntington's disease (Review).Biomedical reports · 2023Review
101 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Mutant huntingtin (HTT) protein causes Huntington disease (HD), an incurable neurological disorder. Silencing mutant HTT using nucleic acids would eliminate the root cause of HD. Developing nucleic acid drugs is challenging, and an ideal clinical approach to gene silencing would combine the simplicity of single-stranded antisense oligonucleotides with the efficiency of RNAi. Here, we describe RNAi by single-stranded siRNAs (ss-siRNAs). ss-siRNAs are potent (>100-fold more than unmodified RNA) and allele-selective (>30-fold) inhibitors of mutant HTT expression in cells derived from HD patients. Strategic placement of mismatched bases mimics micro-RNA recognition and optimizes discrimination between mutant and wild-type alleles. ss-siRNAs require Argonaute protein and function through the RNAi pathway. Intraventricular infusion of ss-siRNA produced selective silencing of the mutant HTT allele throughout the brain in a mouse HD model. These data demonstrate that chemically modified ss-siRNAs function through the RNAi pathway and provide allele-selective compounds for clinical development.
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What OpenQuestion holds
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.