Sistema de Salut de Catalunya
Institut Català de la Salut
[Kagiava A, Sargiannidou I] Neuroscience Department, The Cyprus Institute of Neurology and Genetics and Cyprus School of Molecular Medicine, 1683 Nicosia, Cyprus. [Richter J, Tryfonos C, Christodoulou C] Molecular Virology Department, The Cyprus Institute of Neurology and Genetics and Cyprus School of Molecular Medicine, Nicosia, Cyprus. [Leal-Julià M] Department of Biochemistry and Molecular Biology, Institute of Neurosciences, Barcelona, Spain. Unitat Mixta UAB-VHIR, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Bosch A] Department of Biochemistry and Molecular Biology, Institute of Neurosciences, Barcelona, Spain. Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain. Unitat Mixta UAB-VHIR, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
Vall d'Hebron Barcelona Hospital Campus
2022-05-25T05:59:12Z
2022-05-25T05:59:12Z
2021-11-02
Diseases of the nervous system; Myelin biology and repair; Peripheral nervous system
Enfermedades del sistema nervioso; Biología y reparación de la mielina; Sistema nervioso periférico
Malalties del sistema nerviós; Biologia i reparació de la mielina; Sistema nerviós perifèric
To optimize gene delivery to myelinating Schwann cells we compared clinically relevant AAV serotypes and injection routes. AAV9 and AAVrh10 vectors expressing either EGFP or the neuropathy-associated gene GJB1/Connexin32 (Cx32) under a myelin specific promoter were injected intrathecally or intravenously in wild type and Gjb1-null mice, respectively. Vector biodistribution in lumbar roots and sciatic nerves was higher in AAVrh10 injected mice while EGFP and Cx32 expression rates and levels were similar between the two serotypes. A gradient of biodistribution away from the injection site was seen with both intrathecal and intravenous delivery, while similar expression rates were achieved despite higher vector amounts injected intravenously. Quantified immune cells in relevant tissues were similar to non-injected littermates. Overall, AAV9 and AAVrh10 efficiently transduce Schwann cells throughout the peripheral nervous system with both clinically relevant routes of administration, although AAV9 and intrathecal injection may offer a more efficient approach for treating demyelinating neuropathies.
Generalitat de Catalunya, 2019FI_B2 00061, 2019FI_B2 00061, Fundació la Marató de TV3, 201607.10, Muscular Dystrophy Association, 603003.
Article
Published version
English
Mielina - Metabolisme; Injeccions; Sistema nerviós - Malalties; ANATOMY::Nervous System::Nervous System::Peripheral Nervous System::Peripheral Nerves::Schwann Cells; Other subheadings::Other subheadings::Other subheadings::/metabolism; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Drug Therapy::Drug Administration Routes::Injections::Injections, Spinal; DISEASES::Nervous System Diseases::Demyelinating Diseases; ANATOMÍA::sistema nervioso::sistema nervioso::sistema nervioso periférico::nervios periféricos::células de Schwann; Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::farmacoterapia::vías de administración de medicamentos::inyecciones::inyecciones espinales; ENFERMEDADES::enfermedades del sistema nervioso::enfermedades desmielinizantes
Nature Research
Scientific Reports;11
https://doi.org/10.1038/s41598-021-02694-1
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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