ArticleMolecular therapy. Nucleic acids2019
Targeting RNA-Mediated Toxicity in C9orf72 ALS and/or FTD by RNAi-Based Gene Therapy.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 91 citations in OpenAlex.
- Insights into X-linked Dystonia-Parkinsonism and Spinocerebellar Ataxia type 36 Through the Lens of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.Molecular neurobiology · 2026Review
- Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Review
- Noncoding RNAs are indispensable architects and regulators of biomolecular condensates.Non-coding RNA research · 2026Review
- G-Quadruplexes Abet Neuronal Burnout in ALS and FTD.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- mRNA vaccines and SiRNAs targeting cancer immunotherapy: challenges and opportunities.Discover oncology · 2025Review
- Therapeutic Approaches for C9ORF72-Related ALS: Current Strategies and Future Horizons.International journal of molecular sciences · 2025Review
- AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice.Nature communications · 2025Article
- Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis.Brain sciences · 2025Review
- Targets and Gene Therapy of ALS (Part 1).International journal of molecular sciences · 2025Review
- Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.Translational neurodegeneration · 2025Review
- Tandem repeat disorders: from diagnosis to emerging therapeutic strategies.Encephalitis (Seoul, Korea) · 2025Article
- A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.Nature communications · 2025Article
- The promise of gene therapy in common types of dementia.BioImpacts : BI · 2025Review
- CRISPR-Cas9-mediated homology-directed repair for precise gene editing.Molecular therapy. Nucleic acids · 2024Review
- Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.Molecular neurobiology · 2024Review
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- CRISPR/Cas13d targeting suppresses repeat-associated non-AUG translation of C9orf72 hexanucleotide repeat RNA.The Journal of clinical investigation · 2024Article
9 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
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A hexanucleotide GGGGCC expansion in intron 1 of chromosome 9 open reading frame 72 (C9orf72) gene is the most frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The corresponding repeat-containing sense and antisense transcripts cause a gain of toxicity through the accumulation of RNA foci in the nucleus and deposition of dipeptide-repeat (DPR) proteins in the cytoplasm of the affected cells. We have previously reported on the potential of engineered artificial anti-C9orf72-targeting miRNAs (miC) targeting C9orf72 to reduce the gain of toxicity caused by the repeat-containing transcripts. In the current study, we tested the silencing efficacy of adeno-associated virus (AAV)5-miC in human-derived induced pluripotent stem cell (iPSC) neurons and in an ALS mouse model. We demonstrated that AAV5-miC transduces different types of neuronal cells and can reduce the accumulation of repeat-containing C9orf72 transcripts. Additionally, we demonstrated silencing of C9orf72 in both the nucleus and cytoplasm, which has an added value for the treatment of ALS and/or FTD patients. A proof of concept in an ALS mouse model demonstrated the significant reduction in repeat-containing C9orf72 transcripts and RNA foci after treatment. Taken together, these findings support the feasibility of a gene therapy for ALS and FTD based on the reduction in toxicity caused by the repeat-containing C9orf72 transcripts.
Indexed as
Identifiers
What OpenQuestion holds
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.