ArticleGene therapy2017
AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington's disease.
Article in Gene therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled 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
- StitchR-based dual-AAV delivery strategies enable efficient transduction of defined neural cell populations.Molecular brain · 2026Article
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- CAG-targeting artificial miRNA with reduced off-target risk for efficient lowering of pathogenic polyglutamine proteins.NAR molecular medicine · 2026Article
- Self-inactivating AAV-CRISPR at different ages enables sustained amelioration of Huntington's disease deficits in BAC226Q mice.Science advances · 2026Article
- Gene therapy for huntington's disease: advances, challenges, and future perspectives.Neurogenetics · 2026Review
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.bioRxiv : the preprint server for biology · 2025Article
- shRNAI: A deep neural network for the design of highly potent shRNAs.Molecular therapy. Nucleic acids · 2025Article
- AAV delivery of artificial miRNA targeting MAPT for the reduction of tau pathology in Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- MicroRNAs in neurodegenerative diseases: from molecular mechanisms to clinical biomarkers, detection methods and therapeutic strategies-advances and challenges.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Revolutionizing Huntington's Disease Treatment: Breakthroughs in AAV-Mediated Gene Therapy.Cells · 2025Review
- Exploring immunotherapeutic strategies for neurodegenerative diseases: a focus on Huntington's disease and Prion diseases.Acta pharmacologica Sinica · 2025Review
- Advances in gene and cellular therapeutic approaches for Huntington's disease.Protein & cell · 2025Review
- Genetic therapies for movement disorders - current status.Journal of neurology · 2025Review
- RNA-Targeting CRISPR/CasRx system relieves disease symptoms in Huntington's disease models.Molecular neurodegeneration · 2025Article
- Exon 1-targeting miRNA reduces the pathogenic exon 1 HTT protein in Huntington's disease models.Brain : a journal of neurology · 2024Article
- Review
- 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
- Glucose metabolism in glioma: an emerging sight with ncRNAs.Cancer cell international · 2024Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene. To date, there is no treatment to halt or reverse the course of HD. Lowering of either total or only the mutant HTT expression is expected to have therapeutic benefit. This can be achieved by engineered micro (mi)RNAs targeting HTT transcripts and delivered by an adeno-associated viral (AAV) vector. We have previously showed a miHTT construct to induce total HTT knock-down in Hu128/21 HD mice, while miSNP50T and miSNP67T constructs induced allele-selective HTT knock-down in vitro. In the current preclinical study, the mechanistic efficacy and gene specificity of these selected constructs delivered by an AAV serotype 5 (AAV5) vector was addressed using an acute HD rat model. Our data demonstrated suppression of mutant HTT messenger RNA, which almost completely prevented mutant HTT aggregate formation, and ultimately resulted in suppression of DARPP-32-associated neuronal dysfunction. The AAV5-miHTT construct was found to be the most efficient, although AAV5-miSNP50T demonstrated the anticipated mutant HTT allele selectivity and no passenger strand expression. Ultimately, AAV5-delivered-miRNA-mediated HTT lowering did not cause activation of microglia or astrocytes suggesting no immune response to the AAV5 vector or therapeutic precursor sequences. These preclinical results suggest that using gene therapy to knock-down HTT may provide important therapeutic benefit for HD patients and raised no safety concerns, which supports our ongoing efforts for the development of an RNA interference-based gene therapy product 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.