ArticleNature medicine2019
Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington's disease.
Article in Nature medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.
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Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 216 citations in OpenAlex.
- Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease.Pharmacological research · 2023Pooled it
- Fluid and Imaging Biomarkers in Huntington's Disease.Current neurology and neuroscience reports · 2026Review
- Incorporating AI-optimized zinc finger proteins enhances the efficiencies and targeting ranges of miniature base editors.Nature communications · 2026Article
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- Therapeutic strategies for Huntington's disease: current approaches and future direction.Neurodegenerative disease management · 2026Review
- Self-inactivating AAV-CRISPR at different ages enables sustained amelioration of Huntington's disease deficits in BAC226Q mice.Science advances · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Manipulation of 7‑Finger Zinc Finger Nuclease Increases the Efficiency of Genome Editing in Human Cells.ACS bio & med chem Au · 2025Article
- Molecular and imaging biomarker responses to brain mutant HTT lowering in a mouse model of Huntington disease.Molecular therapy. Nucleic acids · 2025Article
- Natural products proposed for the management of Huntington's disease (HD): a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Suppression of Huntington's Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding.Nature communications · 2025Article
- Review
- Revolutionizing Huntington's Disease Treatment: Breakthroughs in AAV-Mediated Gene Therapy.Cells · 2025Review
- Article
- Epigenome Engineering Using dCas Systems for Biomedical Applications and Biotechnology: Current Achievements, Opportunities and Challenges.International journal of molecular sciences · 2025Review
- Enhanced anti-tumor activity by zinc finger repressor-driven epigenetic silencing of immune checkpoints and TGFBR2 in CAR-T cells and TILs.Molecular therapy. Oncology · 2025Article
- Increased Activity-Dependent Bulk Endocytosis in Huntington's Disease Results From Huntingtin Haploinsufficiency.Journal of neurochemistry · 2025Article
- 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
65 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
51 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion in the huntingtin gene (HTT), which codes for the pathologic mutant HTT (mHTT) protein. Since normal HTT is thought to be important for brain function, we engineered zinc finger protein transcription factors (ZFP-TFs) to target the pathogenic CAG repeat and selectively lower mHTT as a therapeutic strategy. Using patient-derived fibroblasts and neurons, we demonstrate that ZFP-TFs selectively repress >99% of HD-causing alleles over a wide dose range while preserving expression of >86% of normal alleles. Other CAG-containing genes are minimally affected, and virally delivered ZFP-TFs are active and well tolerated in HD neurons beyond 100 days in culture and for at least nine months in the mouse brain. Using three HD mouse models, we demonstrate improvements in a range of molecular, histopathological, electrophysiological and functional endpoints. Our findings support the continued development of an allele-selective ZFP-TF for the treatment of 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.