ArticleMolecular therapy. Nucleic acids2022
A CAG repeat-targeting artificial miRNA lowers the mutant huntingtin level in the YAC128 model of Huntington's disease.
Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.International journal of molecular sciences · 2024Pooled 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
- Double strand breaks drive toxicity in a Huntington's disease mouse model with or without somatic expansion.Nature communications · 2026Article
- CAG-targeting artificial miRNA with reduced off-target risk for efficient lowering of pathogenic polyglutamine proteins.NAR molecular medicine · 2026Article
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.bioRxiv : the preprint server for biology · 2025Article
- Targeting ASK1 signaling in neurodegeneration: molecular insights and therapeutic promise.Apoptosis : an international journal on programmed cell death · 2025Review
- Intrathecal Therapies for Neurodegenerative Diseases: A Review of Current Approaches and the Urgent Need for Advanced Delivery Systems.Biomedicines · 2025Review
- CAG-targeted brain-permeable therapy tested in biallelic humanized polyQ mouse models.Molecular therapy. Nucleic acids · 2025Article
- Double strand breaks drive toxicity in Huntington's disease mice with or without somatic expansion.bioRxiv : the preprint server for biology · 2025Article
- Nerve injury inhibits Oprd1 and Cnr1 transcription through REST in primary sensory neurons.Scientific reports · 2024Article
- Elevated plasma and CSF neurofilament light chain concentrations are stabilized in response to mutant huntingtin lowering in the brains of Huntington's disease mice.Translational neurodegeneration · 2024Article
- From design to cellular processing: Insights into sequencing of vectorized therapeutic small RNAs.Molecular therapy. Nucleic acids · 2024Article
- Sequencing-guided design of genetically encoded small RNAs targeting CAG repeats for selective inhibition of mutantMolecular therapy. Nucleic acids · 2024Article
- 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
- Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Oleuropein enhances proteasomal activity and reduces mutant huntingtin-induced cytotoxicity.Frontiers in pharmacology · 2024Article
- All roads lead to cure: Diversity of oligonucleotides in DM1 therapy.Molecular therapy. Nucleic acids · 2023Article
- Emerging Therapies for Huntington's Disease - Focus on N-Terminal Huntingtin and Huntingtin Exon 1.Biologics : targets & therapy · 2022Review
- [Therapeutic potential of extracellular vesicles in neurological diseases].Nan fang yi ke da xue xue bao = Journal of Southern Medical UniversityReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among the many proposed therapeutic strategies for Huntington's disease (HD), allele-selective therapies are the most desirable but also the most challenging. RNA interference (RNAi) tools that target CAG repeats selectively reduce the mutant huntingtin level in cellular models of HD. The purpose of this study was to test the efficacy, selectivity, and safety of two vector-based RNAi triggers in an animal model of HD. CAG repeat-targeting short hairpin RNA (shRNA) and artificial miRNA (amiRNA) were delivered to the brains of YAC128 mice via intrastriatal injection of AAV5 vectors. Molecular tests demonstrated that both the shRNA and amiRNA reduced the mutant huntingtin level by 50% without influencing endogenous mouse huntingtin. In addition, a concentration-dependent reduction in HTT aggregates in the striatum was observed. In contrast to the shRNA, the amiRNA was well tolerated and did not show signs of toxicity during the course of the experiment up to 20 weeks post injection. Interestingly, amiRNA treatment reduced the spleen weight to values characteristic of healthy (WT) mice and improved motor performance on the static rod test. These preclinical data demonstrate that the CAG-targeting strategy and amiRNA could make an original and valuable contribution to currently used therapeutic approaches for HD.
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