ArticleMolecular therapy : the journal of the American Society of Gene Therapy2008
AAV vector-mediated RNAi of mutant huntingtin expression is neuroprotective in a novel genetic rat model of Huntington's disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 154 citations in OpenAlex.
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- The Molecular Architecture of Neurodegeneration: An Integrative Overview of Convergent Mechanisms.NeuroSci · 2026Review
- 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
- RNA-Targeting CRISPR/CasRx system relieves disease symptoms in Huntington's disease models.Molecular neurodegeneration · 2025Article
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Neurodegenerative Diseases: New Hopes and Perspectives.Current molecular medicine · 2024Review
- Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing.International journal of molecular sciences · 2023Review
- A Specific Mini-Intrabody Mediates Lysosome Degradation of Mutant Huntingtin.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- AAV-based in vivo gene therapy for neurological disorders.Nature reviews. Drug discovery · 2023Review
- Cas9-mediated replacement of expanded CAG repeats in a pig model of Huntington's disease.Nature biomedical engineering · 2023Article
- PET imaging of focused-ultrasound enhanced delivery of AAVs into the murine brain.Theranostics · 2023Article
- Adeno-Associated Viruses for Modeling Neurological Diseases in Animals: Achievements and Prospects.Biomedicines · 2022Review
- Adeno-Associated Viral Vectors as Versatile Tools for Neurological Disorders: Focus on Delivery Routes and Therapeutic Perspectives.Biomedicines · 2022Review
- Current and Possible Future Therapeutic Options for Huntington's Disease.Journal of central nervous system disease · 2022Review
- Review
- Mutant Huntingtin Is Cleared from the Brain via Active Mechanisms in Huntington Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut-Brain Axis.Cellular and molecular gastroenterology and hepatology · 2021Article
- Innovative Therapeutic Approaches for Huntington's Disease: From Nucleic Acids to GPCR-Targeting Small Molecules.Frontiers in cellular neuroscience · 2021Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
We report the characterization of a new rapid-onset model of Huntington's disease (HD) generated by adeno-associated virus (AAV) vector-mediated gene transfer of N-terminal huntingtin (htt) constructs into the rat striatum. Expression of exon 1 of mutant htt containing 70 CAG repeats rapidly led to neuropathological features associated with HD. In addition, we report novel data relating to neuronal transduction of AAV vectors that modulated the phenotype observed in this model. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that AAV vector-mediated expression in the striatum increased by >100-fold as compared to the endogenous htt level. Moreover, AAV vectors exhibited nonuniform transduction patterns in striatal neuronal populations, as well as axonal transport leading to transduction and neuronal cell death in the globus pallidus and substantia nigra (SN). These findings may inform future studies that utilize AAV vectors for neurodegenerative disease modeling. Further, RNA interference (RNAi) of mutant htt expression mediated by virus vector delivery of short hairpin RNAs (shRNAs) ameliorates early-stage disease phenotypes in transgenic mouse models of HD. However, it has not been reported whether shRNA-mediated knockdown of mutant htt expression is neuroprotective. AAV-shRNA was shown to mediate a dramatic knockdown of HD70 expression, preventing striatal neurodegeneration and concomitant motor behavioral impairment. These results provide further support for the use of AAV vector-mediated RNAi as a therapeutic strategy for HD.
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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.