Online-Ressource | |
Verfasst von: | Bartholomä, Cynthia C. [VerfasserIn] |
Arens, Anne [VerfasserIn] | |
Balaggan, Kamaljit S. [VerfasserIn] | |
Yáñez-Muñoz, Rafael J. [VerfasserIn] | |
Montini, Eugenio [VerfasserIn] | |
Howe, Steven J. [VerfasserIn] | |
Paruzynski, Anna [VerfasserIn] | |
Korn, Bernhard [VerfasserIn] | |
Appelt, Jens-Uwe [VerfasserIn] | |
MacNeil, Angus [VerfasserIn] | |
Cesana, Daniela [VerfasserIn] | |
Abel, Ulrich [VerfasserIn] | |
Glimm, Hanno [VerfasserIn] | |
Naldini, Luigi [VerfasserIn] | |
Ali, Robin R. [VerfasserIn] | |
Thrasher, Adrian J. [VerfasserIn] | |
Kalle, Christof von [VerfasserIn] | |
Schmidt, Manfred [VerfasserIn] | |
Titel: | Lentiviral vector integration profiles differ in rodent postmitotic tissues |
Verf.angabe: | Cynthia C Bartholomae, Anne Arens, Kamaljit S Balaggan, Rafael J Yáñez-Muñoz, Eugenio Montini, Steven J Howe, Anna Paruzynski, Bernhard Korn, Jens Uwe Appelt, Angus MacNeil, Daniela Cesana, Ulrich Abel, Hanno Glimm, Luigi Naldini, Robin R Ali, Adrian J Thrasher, Christof von Kalle and Manfred Schmidt |
Jahr: | 2011 |
Umfang: | 8 S. |
Fussnoten: | First published online: 14 December 2016 ; Gesehen am 17.02.2022 |
Titel Quelle: | Enthalten in: Molecular therapy |
Ort Quelle: | Amsterdam : Elsevier, 2000 |
Jahr Quelle: | 2011 |
Band/Heft Quelle: | 19(2011), 4 vom: Apr., Seite 703-710 |
ISSN Quelle: | 1525-0024 |
Abstract: | Lentiviral vectors with self-inactivating (SIN) long terminal repeats (LTRs) are promising for safe and sustained transgene expression in dividing as well as quiescent cells. As genome organization and transcription substantially differs between actively dividing and postmitotic cells in vivo, we hypothesized that genomic vector integration preferences might be distinct between these biological states. We performed integration site (IS) analyses on mouse dividing cells (fibroblasts and hematopoietic progenitor cells (HPCs)) transduced ex vivo and postmitotic cells (eye and brain) transduced in vivo. As expected, integration in dividing cells occurred preferably into gene coding regions. In contrast, postmitotic cells showed a close to random frequency of integration into genes and gene spare long interspersed nuclear elements (LINE). Our studies on the potential mechanisms responsible for the detected differences of lentiviral integration suggest that the lowered expression level of Psip1 reduce the integration frequency in vivo into gene coding regions in postmitotic cells. The motif TGGAA might represent one of the factors for preferred lentiviral integration into mouse and rat Satellite DNA. These observations are highly relevant for the correct assessment of preclinical biosafety studies, indicating that lentiviral vectors are well suited for safe and effective clinical gene transfer into postmitotic tissues. |
DOI: | doi:10.1038/mt.2011.19 |
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/10.1038/mt.2011.19 |
Volltext: https://www.sciencedirect.com/science/article/pii/S1525001616304269 | |
DOI: https://doi.org/10.1038/mt.2011.19 | |
Datenträger: | Online-Ressource |
Sprache: | eng |
Bibliogr. Hinweis: | Erscheint auch als : Druck-Ausgabe: Bartholomä, Cynthia C.: Lentiviral vector integration profiles differ in rodent postmitotic tissues. - 2011 |
K10plus-PPN: | 1789975670 |
Verknüpfungen: | → Zeitschrift |