Full metadata record
DC Field | Value | Language |
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dc.creator | Martier, R. (Raygene) | - |
dc.creator | Liefhebber, J.M. (Jolanda M.) | - |
dc.creator | Garcia-Osta, A. (Ana) | - |
dc.creator | Miniarikova, J. (Jana) | - |
dc.creator | Cuadrado-Tejedor, M. (Mar) | - |
dc.creator | Espelosin, M. (Maria) | - |
dc.creator | Ursua, S. (Susana) | - |
dc.creator | Petry, H. (Harald) | - |
dc.creator | Deventer, S. (Sander) van | - |
dc.creator | Evers, M.M. (Melvin M.) | - |
dc.creator | Konstantinova, P. (Pavlina) | - |
dc.date.accessioned | 2022-06-28T10:05:40Z | - |
dc.date.available | 2022-06-28T10:05:40Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Martier, R. (Raygene); Liefhebber, J.M. (Jolanda M.); Garcia-Osta, A. (Ana); et al. "Targeting RNA-mediated toxicity in C9orf72 ALS and/or FTD by RNAi-based gene therapy". Molecular Therapy - Nucleic Acids. 16, 2019, 26 - 37 | es |
dc.identifier.issn | 2162-2531 | - |
dc.identifier.uri | https://hdl.handle.net/10171/63714 | - |
dc.description.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. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier BV | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | C9orf72 | es_ES |
dc.subject | ALS | es_ES |
dc.subject | FTD | es_ES |
dc.subject | miRNA | es_ES |
dc.subject | Gene therapy | es_ES |
dc.subject | AAV | es_ES |
dc.title | Targeting RNA-mediated toxicity in C9orf72 ALS and/or FTD by RNAi-based gene therapy | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.description.note | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | es_ES |
dc.identifier.doi | 10.1016/j.omtn.2019.02.001 | - |
dadun.citation.endingPage | 37 | es_ES |
dadun.citation.publicationName | Molecular Therapy - Nucleic Acids | es_ES |
dadun.citation.startingPage | 26 | es_ES |
dadun.citation.volume | 16 | es_ES |
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