ArticleChemistry & biology2010
Allele-selective inhibition of huntingtin expression by switching to an miRNA-like RNAi mechanism.
Article in Chemistry & biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed.
- CAG-targeting artificial miRNA with reduced off-target risk for efficient lowering of pathogenic polyglutamine proteins.NAR molecular medicine · 2026Article
- An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.Molecular therapy. Nucleic acids · 2026Article
- CAG-targeted brain-permeable therapy tested in biallelic humanized polyQ mouse models.Molecular therapy. Nucleic acids · 2025Article
- It is Time to Revisit miRNA Therapeutics.Nucleic acid therapeutics · 2025Review
- Sequencing-guided design of genetically encoded small RNAs targeting CAG repeats for selective inhibition of mutantMolecular therapy. Nucleic acids · 2024Article
- A CAG repeat-targeting artificial miRNA lowers the mutant huntingtin level in the YAC128 model of Huntington's disease.Molecular therapy. Nucleic acids · 2022Article
- Haplotype-specific insertion-deletion variations for allele-specific targeting in Huntington's disease.Molecular therapy. Methods & clinical development · 2022Article
- Reexamining assumptions about miRNA-guided gene silencing.Nucleic acids research · 2022Review
- Review
- Emerging Therapies for Huntington's Disease - Focus on N-Terminal Huntingtin and Huntingtin Exon 1.Biologics : targets & therapy · 2022Review
- Difficulties translating antisense-mediated activation of Frataxin expression from cell culture to mice.RNA biology · 2022Article
- The emerging roles of long non-coding RNAs in polyglutamine diseases.Journal of cellular and molecular medicine · 2021Review
- Selective suppression of polyglutamine-expanded protein by lipid nanoparticle-delivered siRNA targeting CAG expansions in the mouse CNS.Molecular therapy. Nucleic acids · 2021Article
- What, When and How to Measure-Peripheral Biomarkers in Therapy of Huntington's Disease.International journal of molecular sciences · 2021Review
- Artificial miRNAs targeting CAG repeat expansion in ORFs cause rapid deadenylation and translation inhibition of mutant transcripts.Cellular and molecular life sciences : CMLS · 2021Article
- Universal RNAi Triggers for the Specific Inhibition of Mutant Huntingtin, Atrophin-1, Ataxin-3, and Ataxin-7 Expression.Molecular therapy. Nucleic acids · 2020Article
- Potent and sustained huntingtin lowering via AAV5 encoding miRNA preserves striatal volume and cognitive function in a humanized mouse model of Huntington disease.Nucleic acids research · 2020Article
- Limits of using oligonucleotides for allele-selective inhibition at trinucleotide repeat sequences - targeting the CAG repeat within ataxin-1.Nucleosides, nucleotides & nucleic acids · 2020Article
- Duplex RNAs and ss-siRNAs Block RNA Foci Associated with Fuchs' Endothelial Corneal Dystrophy.Nucleic acid therapeutics · 2019Article
- The Emerging Role of microRNAs in Polyglutamine Diseases.Frontiers in molecular neuroscience · 2019Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Inhibiting expression of huntingtin (HTT) protein is a promising strategy for treating Huntington's disease (HD), but indiscriminant inhibition of both wild-type and mutant alleles may lead to toxicity. An ideal silencing agent would block expression of mutant HTT while leaving expression of wild-type HTT intact. We observe that fully complementary duplex RNAs targeting the expanded CAG repeat within HTT mRNA block expression of both alleles. Switching the RNAi mechanism toward that used by miRNAs by introducing one or more mismatched bases into these duplex RNAs leads to potent (<10 nM) and highly selective (>30-fold relative to wild-type HTT) inhibition of mutant HTT expression in patient-derived cells. Potent, allele selective inhibition of HTT by mismatched RNAs provides a new option for developing HD therapeutics.
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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.