| |  Online-Ressource |
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| Verfasst von: | Kremer, Lukas P. M. [VerfasserIn]  |
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| | Cerrizuela, Santiago [VerfasserIn] |
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| | Dehler, Sascha [VerfasserIn] |
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| | Stiehl, Thomas [VerfasserIn] |
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| | Weinmann, Jonas [VerfasserIn] |
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| | Abendroth, Heike [VerfasserIn] |
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| | Kleber, Susanne [VerfasserIn] |
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| | Laure, Alexander [VerfasserIn] |
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| | El Andari, Jihad [VerfasserIn] |
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| | Anders, Simon [VerfasserIn] |
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| | Marciniak-Czochra, Anna [VerfasserIn] |
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| | Grimm, Dirk [VerfasserIn] |
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| | Martín-Villalba, Ana [VerfasserIn] |
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| Titel: | High throughput screening of novel AAV capsids identifies variants for transduction of adult NSCs within the subventricular zone |
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| Verf.angabe: | Lukas P.M. Kremer, Santiago Cerrizuela, Sascha Dehler, Thomas Stiehl, Jonas Weinmann, Heike Abendroth, Susanne Kleber, Alexander Laure, Jihad El Andari, Simon Anders, Anna Marciniak-Czochra, Dirk Grimm, and Ana Martin-Villalba |
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| E-Jahr: | 2021 |
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| Jahr: | 4 September 2021 |
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| Umfang: | 18 S. |
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| Fussnoten: | Gesehen am 21.09.2022 |
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| Titel Quelle: | Enthalten in: Molecular therapy. Methods & clinical development |
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| Ort Quelle: | New York, NY : Nature Publishing Group, 2014 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 23(2021) vom: 10. Dez., Seite 33-50 |
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| ISSN Quelle: | 2329-0501 |
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| Abstract: | The adult mammalian brain entails a reservoir of neural stem cells (NSCs) generating glial cells and neurons. However, NSCs become increasingly quiescent with age, which hampers their regenerative capacity. New means are therefore required to genetically modify adult NSCs for re-enabling endogenous brain repair. Recombinant adeno-associated viruses (AAVs) are ideal gene-therapy vectors due to an excellent safety profile and high transduction efficiency. We thus conducted a high-throughput screening of 177 intraventricularly injected barcoded AAV variants profiled by RNA sequencing. Quantification of barcoded AAV mRNAs identified two synthetic capsids, peptide-modified derivative of wild-type AAV9 (AAV9_A2) and peptide-modified derivative of wild-type AAV1 (AAV1_P5), both of which transduce active and quiescent NSCs. Further optimization of AAV1_P5 by judicious selection of the promoter and dose of injected viral genomes enabled labeling of 30%-60% of the NSC compartment, which was validated by fluorescence-activated cell sorting (FACS) analyses and single-cell RNA sequencing. Importantly, transduced NSCs readily produced neurons. The present study identifies AAV variants with a high regional tropism toward the ventricular-subventricular zone (v-SVZ) with high efficiency in targeting adult NSCs, thereby paving the way for preclinical testing of regenerative gene therapy. |
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| DOI: | doi:10.1016/j.omtm.2021.07.001 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.omtm.2021.07.001 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S2329050121001182 |
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| | DOI: https://doi.org/10.1016/j.omtm.2021.07.001 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | AAV |
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| | adeno-associated virus |
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| | adult neurogenesis |
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| | gene therapy |
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| | neural stem cells |
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| | single-cell RNA-seq |
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| | v-SVZ |
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| | ventricular-subventricular zone |
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| K10plus-PPN: | 1817201808 |
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| Verknüpfungen: | → Zeitschrift |
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High throughput screening of novel AAV capsids identifies variants for transduction of adult NSCs within the subventricular zone / Kremer, Lukas P. M. [VerfasserIn]; 4 September 2021 (Online-Ressource)
