ArticlePloS one2014
Allele-specific silencing of mutant huntingtin in rodent brain and human stem cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Molecular interplay between Non-coding RNAs and BDNF in Neurodegenerative Disorders: a systematic review.Molecular biology reports · 2026Pooled it
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.bioRxiv : the preprint server for biology · 2025Article
- Allele-specific RNAi therapy corrects an extracellular matrix defect in Schuurs-Hoeijmakers syndrome.American journal of human genetics · 2025Article
- HAP40 modulates mutant Huntingtin aggregation and toxicity in Huntington's disease mice.Cell death & disease · 2024Article
- Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- When synthetic biology meets medicine.Life medicine · 2024Review
- Mono- and Biallelic Inactivation of Huntingtin Gene in Patient-Specific Induced Pluripotent Stem Cells Reveal HTT Roles in Striatal Development and Neuronal Functions.Journal of Huntington's disease · 2024Article
- Optimal delivery of RNA interference by viral vectors for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Gene replacement therapy in two Golgi-retained CMT1X mutants before and after the onset of demyelinating neuropathy.Molecular therapy. Methods & clinical development · 2023Article
- CRISPR-Based Genome-Editing Tools for Huntington's Disease Research and Therapy.Neuroscience bulletin · 2022Review
- Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington's disease models.Nature communications · 2022Article
- Development of versatile allele-specific siRNAs able to silence all the dominant dynamin 2 mutations.Molecular therapy. Nucleic acids · 2022Article
- Allele-specific silencing by RNAi of R92Q and R173W mutations in cardiac troponin T.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- New Avenues for the Treatment of Huntington's Disease.International journal of molecular sciences · 2021Review
- Maximizing lentiviral vector gene transfer in the CNS.Gene therapy · 2021Article
- Molecular Strategies to Target Protein Aggregation in Huntington's Disease.Frontiers in molecular biosciences · 2021Review
- Prion-like mechanisms in neurodegenerative disease: Implications for Huntington's disease therapy.Stem cells translational medicine · 2020Review
- 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
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin (HTT) protein and for which there is no cure. Although suppression of both wild type and mutant HTT expression by RNA interference is a promising therapeutic strategy, a selective silencing of mutant HTT represents the safest approach preserving WT HTT expression and functions. We developed small hairpin RNAs (shRNAs) targeting single nucleotide polymorphisms (SNP) present in the HTT gene to selectively target the disease HTT isoform. Most of these shRNAs silenced, efficiently and selectively, mutant HTT in vitro. Lentiviral-mediated infection with the shRNAs led to selective degradation of mutant HTT mRNA and prevented the apparition of neuropathology in HD rat's striatum expressing mutant HTT containing the various SNPs. In transgenic BACHD mice, the mutant HTT allele was also silenced by this approach, further demonstrating the potential for allele-specific silencing. Finally, the allele-specific silencing of mutant HTT in human embryonic stem cells was accompanied by functional recovery of the vesicular transport of BDNF along microtubules. These findings provide evidence of the therapeutic potential of allele-specific RNA interference for HD.
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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.