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Status: Bibliographieeintrag

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Verfasst von:Hölscher, Christina D. [VerfasserIn]   i
 Sonntag, Florian [VerfasserIn]   i
 Henrich, Katharina [VerfasserIn]   i
 Chen, Qingxin [VerfasserIn]   i
 Beneke, Jürgen [VerfasserIn]   i
 Matula, Petr [VerfasserIn]   i
 Rohr, Karl [VerfasserIn]   i
 Kaderali, Lars [VerfasserIn]   i
 Beil, Nina [VerfasserIn]   i
 Erfle, Holger [VerfasserIn]   i
 Kleinschmidt, Jürgen [VerfasserIn]   i
 Müller, Martin [VerfasserIn]   i
Titel:The SUMOylation pathway restricts gene transduction by adeno-associated viruses
Verf.angabe:Christina Hölscher, Florian Sonntag, Katharina Henrich, Qingxin Chen, Jürgen Beneke, Petr Matula, Karl Rohr, Lars Kaderali, Nina Beil, Holger Erfle, Jürgen A. Kleinschmidt, Martin Müller
E-Jahr:2015
Jahr:December 1, 2015
Umfang:23 S.
Fussnoten:Gesehen am 08.09.2020
Titel Quelle:Enthalten in: Public Library of SciencePLoS pathogens
Ort Quelle:Lawrence, Kan. : PLoS, 2005
Jahr Quelle:2015
Band/Heft Quelle:11(2015,12) Artikel-Nummer e1005281, 23 Seiten
ISSN Quelle:1553-7374
Abstract:Adeno-associated viruses are members of the genus dependoviruses of the parvoviridae family. AAV vectors are considered promising vectors for gene therapy and genetic vaccination as they can be easily produced, are highly stable and non-pathogenic. Nevertheless, transduction of cells in vitro and in vivo by AAV in the absence of a helper virus is comparatively inefficient requiring high multiplicity of infection. Several bottlenecks for AAV transduction have previously been described, including release from endosomes, nuclear transport and conversion of the single stranded DNA into a double stranded molecule. We hypothesized that the bottlenecks in AAV transduction are, in part, due to the presence of host cell restriction factors acting directly or indirectly on the AAV-mediated gene transduction. In order to identify such factors we performed a whole genome siRNA screen which identified a number of putative genes interfering with AAV gene transduction. A number of factors, yielding the highest scores, were identified as members of the SUMOylation pathway. We identified Ubc9, the E2 conjugating enzyme as well as Sae1 and Sae2, enzymes responsible for activating E1, as factors involved in restricting AAV. The restriction effect, mediated by these factors, was validated and reproduced independently. Our data indicate that SUMOylation targets entry of AAV capsids and not downstream processes of uncoating, including DNA single strand conversion or DNA damage signaling. We suggest that transiently targeting SUMOylation will enhance application of AAV in vitro and in vivo.
DOI:doi:10.1371/journal.ppat.1005281
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/10.1371/journal.ppat.1005281
 Verlag: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005281
 DOI: https://doi.org/10.1371/journal.ppat.1005281
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Capsids
 HeLa cells
 Host cells
 Library screening
 Luciferase
 Small interfering RNA
 SUMOylation
 Transfection
K10plus-PPN:172910097X
Verknüpfungen:→ Zeitschrift

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