| |  Online-Ressource |
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| Verfasst von: | Becker, Jonas [VerfasserIn]  |
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| | Stanifer, Megan [VerfasserIn] |
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| | Leist, Sarah Rebecca [VerfasserIn] |
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| | Stolp-Rastätter, Bettina [VerfasserIn] |
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| | Maiakovska, Olena [VerfasserIn] |
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| | West, Ande [VerfasserIn] |
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| | Wiedtke, Ellen [VerfasserIn] |
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| | Börner, Kathleen [VerfasserIn] |
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| | Ghanem, Ali [VerfasserIn] |
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| | Ambiel, Ina [VerfasserIn] |
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| | Tse, Longping Victor [VerfasserIn] |
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| | Fackler, Oliver Till [VerfasserIn] |
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| | Baric, Ralph Steven [VerfasserIn] |
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| | Boulant, Steeve [VerfasserIn] |
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| | Grimm, Dirk [VerfasserIn] |
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| Titel: | Ex vivo and in vivo suppression of SARS-CoV-2 with combinatorial AAV/RNAi expression vectors |
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| Verf.angabe: | Jonas Becker, Megan Lynn Stanifer, Sarah Rebecca Leist, Bettina Stolp, Olena Maiakovska, Ande West, Ellen Wiedtke, Kathleen Börner, Ali Ghanem, Ina Ambiel, Longping Victor Tse, Oliver Till Fackler, Ralph Steven Baric, Steeve Boulant, and Dirk Grimm |
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| E-Jahr: | 2022 |
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| Jahr: | 14 January 2022 |
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| Umfang: | 19 S. |
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| Fussnoten: | Gesehen am 20.07.2022 |
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| Titel Quelle: | Enthalten in: Molecular therapy |
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| Ort Quelle: | Amsterdam : Elsevier, 2000 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 30(2022), 5 vom: Mai, Seite 2005-2023 |
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| ISSN Quelle: | 1525-0024 |
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| Abstract: | Despite rapid development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant modalities to curb the pandemic by directly attacking the virus on a genetic level remain highly desirable and are urgently needed. Here we comprehensively illustrate the capacity of adeno-associated virus (AAV) vectors co-expressing a cocktail of three short hairpin RNAs (shRNAs; RNAi triggers) directed against the SARS-CoV-2 RdRp and N genes as versatile and effective antiviral agents. In cultured monkey cells and human gut organoids, our most potent vector, SAVIOR (SARS virus repressor), suppressed SARS-CoV-2 infection to background levels. Strikingly, in control experiments using single shRNAs, multiple SARS-CoV-2 escape mutants quickly emerged from infected cells within 24-48 h. Importantly, such adverse viral adaptation was fully prevented with the triple-shRNA AAV vector even during long-term cultivation. In addition, AAV-SAVIOR efficiently purged SARS-CoV-2 in a new model of chronically infected human intestinal cells. Finally, intranasal AAV-SAVIOR delivery using an AAV9 capsid moderately diminished viral loads and/or alleviated disease symptoms in hACE2-transgenic or wild-type mice infected with human or mouse SARS-CoV-2 strains, respectively. Our combinatorial and customizable AAV/RNAi vector complements ongoing global efforts to control the coronavirus disease 2019 (COVID-19) pandemic and holds great potential for clinical translation as an original and flexible preventive or therapeutic antiviral measure. |
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| DOI: | doi:10.1016/j.ymthe.2022.01.024 |
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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 ; Verlag: https://doi.org/10.1016/j.ymthe.2022.01.024 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S1525001622000247 |
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| | DOI: https://doi.org/10.1016/j.ymthe.2022.01.024 |
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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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| | antiviral RNAi |
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| | COVID-19 |
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| | mutational escape |
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| | RNAi |
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| | SARS-CoV-2 |
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| K10plus-PPN: | 181100119X |
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| Verknüpfungen: | → Zeitschrift |
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Ex vivo and in vivo suppression of SARS-CoV-2 with combinatorial AAV/RNAi expression vectors / Becker, Jonas [VerfasserIn]; 14 January 2022 (Online-Ressource)
