ArticlePloS one2009
Design of RNAi hairpins for mutation-specific silencing of ataxin-7 and correction of a SCA7 phenotype.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
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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
35 citing papers in PubMed, 61 citations in OpenAlex.
- Experimental Models to Study Polyglutamine Spinocerebellar Ataxias: From Mechanisms to Therapeutic Developments.Cerebellum (London, England) · 2026Review
- Ataxia in Africa: current efforts and recommendations.Annals of medicine and surgery (2012) · 2025Review
- Therapeutic Strategies for Spinocerebellar Ataxia Type 1.Biomolecules · 2023Review
- Combinational treatments of RNA interference and extracellular vesicles in the spinocerebellar ataxia.Frontiers in molecular neuroscience · 2022Review
- Molecular and electrophysiological features of spinocerebellar ataxia type seven in induced pluripotent stem cells.PloS one · 2021Article
- Review
- Exploring the Potential of Small Molecule-Based Therapeutic Approaches for Targeting Trinucleotide Repeat Disorders.Molecular neurobiology · 2020Review
- Recent advances in molecular therapies for neurological disease: triplet repeat disorders.Human molecular genetics · 2019Review
- Spinocerebellar ataxia: an update.Journal of neurology · 2019Review
- Knockdown and replacement therapy mediated by artificial mirtrons in spinocerebellar ataxia 7.Nucleic acids research · 2017Article
- Article
- An understanding of spinocerebellar ataxia.The Indian journal of medical research · 2015Article
- Allele-specific silencing of mutant Ataxin-7 in SCA7 patient-derived fibroblasts.European journal of human genetics : EJHG · 2014Article
- Nonallele specific silencing of ataxin-7 improves disease phenotypes in a mouse model of SCA7.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Oligonucleotide-based strategies to combat polyglutamine diseases.Nucleic acids research · 2014Review
- Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias.Cerebellum (London, England) · 2014Article
- Small non-coding RNAs add complexity to the RNA pathogenic mechanisms in trinucleotide repeat expansion diseases.Frontiers in molecular neuroscience · 2013Review
- Non-coding RNAs in crop genetic modification: considerations and predictable environmental risk assessments (ERA).Molecular biotechnology · 2013Review
- Mechanisms of RNA-induced toxicity in CAG repeat disorders.Cell death & disease · 2013Review
- Recent advances in RNA interference therapeutics for CNS diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2013Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Spinocerebellar ataxia type 7 is a polyglutamine disorder caused by an expanded CAG repeat mutation that results in neurodegeneration. Since no treatment exists for this chronic disease, novel therapies such post-transcriptional RNA interference-based gene silencing are under investigation, in particular those that might enable constitutive and tissue-specific silencing, such as expressed hairpins. Given that this method of silencing can be abolished by the presence of nucleotide mismatches against the target RNA, we sought to identify expressed RNA hairpins selective for silencing the mutant ataxin-7 transcript using a linked SNP. By targeting both short and full-length tagged ataxin-7 sequences, we show that mutation-specific selectivity can be obtained with single nucleotide mismatches to the wild-type RNA target incorporated 3' to the centre of the active strand of short hairpin RNAs. The activity of the most effective short hairpin RNA incorporating the nucleotide mismatch at position 16 was further studied in a heterozygous ataxin-7 disease model, demonstrating significantly reduced levels of toxic mutant ataxin-7 protein with decreased mutant protein aggregation and retention of normal wild-type protein in a non-aggregated diffuse cellular distribution. Allele-specific mutant ataxin7 silencing was also obtained with the use of primary microRNA mimics, the most highly effective construct also harbouring the single nucleotide mismatch at position 16, corroborating our earlier findings. Our data provide understanding of RNA interference guide strand anatomy optimised for the allele-specific silencing of a polyglutamine mutation linked SNP and give a basis for the use of allele-specific RNA interference as a viable therapeutic approach for spinocerebellar ataxia 7.
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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.