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ResearchIn-Press PreviewNeuroscienceTherapeutics
Open Access | 10.1172/JCI159316
1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Goldberg, E.
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Kremer, E.
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1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2IGF, CNRS 5203 INSERM U661, Montpellier, France
3Institut de Génétique Moléculaire de Montpellier, CNRS, Montpellier, France
4Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America
7Gene Therapy and Regulation of Gene Expression Program, CIMA University of Navarra, Pamplona, Spain
8Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Rubinstein, M.
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Published May 16, 2023 - More info
Dravet syndrome (DS), an intractable childhood epileptic encephalopathy with a high fatality rate, is typically caused by loss-of-function mutations in one allele of SCN1A, which encodes NaV1.1, a 250-kDa voltage-gated sodium channel. In contrast to other epilepsies, pharmaceutical treatment for DS is limited. Here, we demonstrate that viral vector-mediated delivery of a codon-modified SCN1A open reading frame into the brain improves DS comorbidities in juvenile and adolescent DS mice (Scn1aA1783V/WT). Notably, bilateral vector injections into the hippocampus and/or the thalamus of DS mice increased survival, reduced the occurrence of epileptic spikes, provided protection from thermally-induced seizures, corrected background electrocorticography activity and behavioral deficits, and restored hippocampal inhibition. Together, our results provide a proof-of-concept for the potential of SCN1A delivery as a therapeutic approach for infants and adolescents with DS-associated comorbidities.