ArticleCurrent biology : CB2009
Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients.
Article in Current biology : CB, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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Who cites it
136 citing papers in PubMed, 248 citations in OpenAlex.
- Allele-selective von Willebrand factor silencing.Research and practice in thrombosis and haemostasis · 2026Article
- Development of Antisense Gapmers for the Treatment of Huntington's Disease.Methods in molecular biology (Clifton, N.J.) · 2026Article
- CRISPR-based gene therapy for huntington's disease: current advances and future prospects.Neurogenetics · 2025Review
- DurableMolecular therapy. Nucleic acids · 2025Article
- The future of siRNA-mediated approaches to treat von Willebrand disease.Expert review of hematology · 2025Review
- Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.Molecular neurobiology · 2024Review
- Advancements in surgical treatments for Huntington disease: From pallidotomy to experimental therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutantMolecular therapy. Nucleic acids · 2024Article
- Latest advances on new promising molecular-based therapeutic approaches for Huntington's disease.Journal of translational internal medicine · 2024Article
- Allele-specific quantitation of ATXN3 and HTT transcripts in polyQ disease models.BMC biology · 2023Article
- Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington's disease models.Nature communications · 2022Article
- Potential disease-modifying therapies for Huntington's disease: lessons learned and future opportunities.The Lancet. Neurology · 2022Review
- Haplotype-specific insertion-deletion variations for allele-specific targeting in Huntington's disease.Molecular therapy. Methods & clinical development · 2022Article
- shRNAs Targeting a CommonInternational journal of molecular sciences · 2022Article
- [Disease-modifying treatment approaches in Huntington disease : Past and future].Der Nervenarzt · 2022Review
- SUPT4H1-edited stem cell therapy rescues neuronal dysfunction in a mouse model for Huntington's disease.NPJ Regenerative medicine · 2022Article
- Gene Therapy for Huntington's Disease: The Final Strategy for a Cure?Journal of movement disorders · 2022Article
- Allele-Specific Knockdown of Mutant Huntingtin Protein via Editing at Coding Region Single Nucleotide Polymorphism Heterozygosities.Human gene therapy · 2022Article
- Cerebral Organoids and Antisense Oligonucleotide Therapeutics: Challenges and Opportunities.Frontiers in molecular neuroscience · 2022Review
- Structurally constrained phosphonate internucleotide linkage impacts oligonucleotide-enzyme interaction, and modulates siRNA activity and allele specificity.Nucleic acids research · 2021Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Among dominant neurodegenerative disorders, Huntington's disease (HD) is perhaps the best candidate for treatment with small interfering RNAs (siRNAs) [1-9]. Invariably fatal, HD is caused by expansion of a CAG repeat in the Huntingtin gene, creating an extended polyglutamine tract that makes the Huntingtin protein toxic [10]. Silencing mutant Huntingtin messenger RNA (mRNA) should provide therapeutic benefit, but normal Huntingtin likely contributes to neuronal function [11-13]. No siRNA strategy can yet distinguish among the normal and disease Huntingtin alleles and other mRNAs containing CAG repeats [14]. siRNAs targeting the disease isoform of a heterozygous single-nucleotide polymorphism (SNP) in Huntingtin provide an alternative [15-19]. We sequenced 22 predicted SNP sites in 225 human samples corresponding to HD and control subjects. We find that 48% of our patient population is heterozygous at a single SNP site; one isoform of this SNP is associated with HD. Several other SNP sites are frequently heterozygous. Consequently, five allele-specific siRNAs, corresponding to just three SNP sites, could be used to treat three-quarters of the United States and European HD patient populations. We have designed and validated selective siRNAs for the three SNP sites, laying the foundation for allele-specific RNA interference (RNAi) therapy for HD.
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