Viral-mediated temporally controlled dopamine production in a rat model of Parkinson disease
| العنوان: | Viral-mediated temporally controlled dopamine production in a rat model of Parkinson disease |
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| المؤلفون: | Li, X.-G., Okada, T., Kodera, M., Nara, Y., Takino, N., Muramatsu, C., Ikeguchi, K., Urano, F., Ichinose, Hiroshi, Metzger, D., Chambon, P., Nakano, I., Ozawa, K., Muramatsu, S.-I. |
| المساهمون: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Molecular Therapy Molecular Therapy, Cell Press, 2006, 13 (1), pp.160-6. ⟨10.1016/j.ymthe.2005.08.009⟩ Molecular Therapy, Nature Publishing Group, 2006, 13 (1), pp.160-6. ⟨10.1016/j.ymthe.2005.08.009⟩ |
| بيانات النشر: | Elsevier BV, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Male, MESH: Integrases, Genetic enhancement, Dopamine, MESH: Neurons, MESH: Dependovirus, medicine.disease_cause, MESH: Corpus Striatum, Levodopa, Mice, 0302 clinical medicine, Estrogen Receptor Modulators, MESH: Genetic Vectors, Drug Discovery, MESH: Animals, MESH: Tyrosine 3-Monooxygenase, MESH: Estrogen Receptor alpha, Adeno-associated virus, MESH: Levodopa, Regulation of gene expression, Neurons, Recombination, Genetic, 0303 health sciences, Parkinson Disease, Dependovirus, MESH: Estrogen Receptor Modulators, 3. Good health, Aromatic-L-Amino-Acid Decarboxylases, Molecular Medicine, MESH: Aromatic-L-Amino-Acid Decarboxylases, MESH: Recombination, Genetic, medicine.drug, MESH: Stereotyped Behavior, MESH: Rats, Tyrosine 3-Monooxygenase, Transgene, Genetic Vectors, Cre recombinase, MESH: Dopamine, Biology, Cell Line, 03 medical and health sciences, Viral Proteins, medicine, Genetics, Animals, Humans, Rats, Wistar, MESH: Mice, Molecular Biology, 030304 developmental biology, Pharmacology, MESH: Humans, Tyrosine hydroxylase, Integrases, Estrogen Receptor alpha, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Rats, Wistar, Genetic Therapy, MESH: Viral Proteins, Molecular biology, MESH: Male, Corpus Striatum, MESH: Cell Line, Rats, Disease Models, Animal, Tamoxifen, MESH: Tamoxifen, MESH: Disease Models, Animal, MESH: Gene Therapy, Stereotyped Behavior, Estrogen receptor alpha, MESH: Parkinson Disease, 030217 neurology & neurosurgery |
| الوصف: | International audience; Regulation of gene expression is necessary to avoid possible adverse effects of gene therapy due to excess synthesis of transgene products. To reduce transgene expression, we developed a viral vector-mediated somatic regulation system using inducible Cre recombinase. A recombinant adeno-associated virus (AAV) vector expressing Cre recombinase fused to a mutated ligand-binding domain of the estrogen receptor alpha (CreER(T2)) was delivered along with AAV vectors expressing dopamine-synthesizing enzymes to rats of a Parkinson disease model. Treatment with 4-hydroxytamoxifen, a synthetic estrogen receptor modulator, activated Cre recombinase within the transduced neurons and induced selective excision of the tyrosine hydroxylase (TH) coding sequence flanked by loxP sites, leading to a reduction in transgene-mediated dopamine synthesis. Using this strategy, aromatic L-amino acid decarboxylase (AADC) activity was retained so that l-3,4-dihydroxyphenylalanine (L-dopa), a substrate for AADC, could be converted to dopamine in the striatum and the therapeutic effects of L-dopa preserved, even after reduction of TH expression in the case of dopamine overproduction. Our data demonstrate that viral vector-mediated inducible Cre recombinase can serve as an in vivo molecular switch, allowing spatial and temporal control of transgene expression, thereby potentially increasing the safety of gene therapy. |
| تدمد: | 1525-0016 1525-0024 |
| DOI: | 10.1016/j.ymthe.2005.08.009 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0093e6f4805eebf8fc2f4d9d106d6a3a |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0093e6f4805eebf8fc2f4d9d106d6a3a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15250016 15250024 |
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| DOI: | 10.1016/j.ymthe.2005.08.009 |