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Introduction Destination: Head2 Item: Title: 2. Methods Destination: Head3 Children: Item: Title: 2.1. Vector construction, production, and titration Destination: Head4 Item: Title: 2.2. Animal procedures Destination: Head5 Item: Title: 2.3. TP activity and nucleoside determination Destination: Head6 Item: Title: 2.4. Vector copy number determination Destination: Head7 Item: Title: 2.5. Motor performance Destination: Head8 Item: Title: 2.6. Magnetic resonance imaging Destination: Head9 Item: Title: 2.7. Mitochondrial isolation and dNTP determination Destination: Head10 Item: Title: 2.8. Mitochondrial DNA copy number analysis Destination: Head11 Item: Title: 2.9. Histochemical staining of small intestine Destination: Head12 Item: Title: 2.10. Statistical analysis Destination: Head13 Item: Title: 2.11. Role of funding source Destination: Head14 Item: Title: 3. Results Destination: Head15 Children: Item: Title: 3.1. Pharmacokinetics of dThd and dUrd in the murine model Destination: Head16 Item: Title: 3.2. AAV-TYMP treatment limits nucleoside stress in chronically dThd/dUrd -exposed dKO mice Destination: Head17 Item: Title: 3.3. AAV-TYMP treatment induces increased TP activity in liver Destination: Head18 Item: Title: 3.4. Histological analysis of small intestine and mtDNA copy number Destination: Head19 Item: Title: 3.5. Effect of the AAV-TYMP treatment on neurological phenotype Destination: Head20 Item: Title: 3.6. AAV-TYMP treatment normalized the mitochondrial dNTP balance Destination: Head21 Item: Title: 4. Discussion Destination: Head22 Item: Title: Contributors Destination: Head23 Item: Title: Declaration of Competing Interests Destination: Head24 Children: Item: Title: Acknowledgments Destination: Head25 Item: Title: Data sharing statement Destination: Head26 Item: Title: Supplementary materials Destination: Head27 Children: Item: Title: References Destination: Head28 Info: Title: Efficacy of adeno-associated virus gene therapy in a MNGIE murine model enhanced by chronic exposure to nucleosides Author: Ferran Vila-Julià Subject: EBioMedicine, 62 (2020) 103133. doi:10.1016/j.ebiom.2020.103133 Keywords: "MNGIE"; "Gene therapy"; "Nucleosides"; "Mitochondrial disease"; "Thymidine phosphorylase" Creator: Elsevier Producer: Acrobat Distiller 10.1.10 (Windows) CreationDate: Sat Nov 21 01:14:02 CET 2020 ModDate: Sat Nov 21 01:14:35 CET 2020 ID: 0x74b1679fa50bfa9a672d7e23da5b046a, 0x82971445c6d0b84ba9bcdb79dea6eeaf Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: 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EBioMedicine, 62 (2020) 103133. doi:10.1016/j.ebiom.2020.103133 MNGIE Gene therapy Nucleosides Mitochondrial disease Thymidine phosphorylase Efficacy of adeno-associated virus gene therapy in a MNGIE murine model enhanced by chronic exposure to nucleosides Ferran Vila-Julià Raquel Cabrera-Pérez Yolanda Cámara Miguel Molina-Berenguer Silvia Lope-Piedrafita Michio Hirano Federico Mingozzi Javier Torres-Torronteras Ramon Martí uuid:fd8cfc10-4791-4a8b-8025-00abb91efa0c uuid:628c3fdc-9b30-4c6b-b359-a0b872feb928 journal © 2020 The Authors. Published by Elsevier B.V. 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Subtype: Link Rect: 317, 464, 552, 470 Annotation: Subtype: Link Rect: 317, 456, 474, 462 Annotation: Subtype: Link Rect: 317, 448, 552, 454 Annotation: Subtype: Link Rect: 317, 440, 552, 446 Annotation: Subtype: Link Rect: 317, 432, 407, 438 Annotation: Subtype: Link Rect: 317, 424, 552, 430 Annotation: Subtype: Link Rect: 317, 416, 552, 422 Annotation: Subtype: Link Rect: 317, 408, 397, 415 Annotation: Subtype: Link Rect: 317, 400, 552, 407 Annotation: Subtype: Link Rect: 317, 392, 393, 399 Annotation: Subtype: Link Rect: 317, 384, 552, 391 Annotation: Subtype: Link Rect: 317, 376, 552, 383 Annotation: Subtype: Link Rect: 317, 368, 407, 375 Annotation: Subtype: Link Rect: 317, 360, 552, 367 Annotation: Subtype: Link Rect: 317, 352, 552, 359 Annotation: Subtype: Link Rect: 317, 344, 441, 351 Checksum: b137a393 Type: CRC32 Checksum: fbf0bf3eb21766465839de6cbc43dd07 Type: MD5 Checksum: 0dde26ee01f131a2344f8fb87d1aa56cb447ae33 Type: SHA-1 Checksum: 55e37b8dd01ec15e30fd492aaaf487716d878c479ccdffcc3a4ca3cb8be9f6f5 Type: SHA-256