dc.contributor.author
Schaar, Katrin
dc.contributor.author
Geisler, Anja
dc.contributor.author
Kraus, Milena
dc.contributor.author
Pinkert, Sandra
dc.contributor.author
Pryshliak, Markian
dc.contributor.author
Spencer, Jacqueline F.
dc.contributor.author
Tollefson, Ann E.
dc.contributor.author
Ying, Baoling
dc.contributor.author
Kurreck, Jens
dc.contributor.author
Wold, William S.
dc.contributor.author
Klopfleisch, Robert
dc.contributor.author
Toth, Karoly
dc.contributor.author
Fechner, Henry
dc.date.accessioned
2018-06-08T10:18:30Z
dc.date.available
2017-09-18T10:38:07.330Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20218
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-23523
dc.description.abstract
Infections of immunocompromised patients with human adenoviruses (hAd) can
develop into life-threatening conditions, whereas drugs with anti-adenoviral
efficiency are not clinically approved and have limited efficacy. Small
double-stranded RNAs that induce RNAi represent a new class of promising anti-
adenoviral therapeutics. However, as yet, their efficiency to treat hAd5
infections has only been investigated in vitro. In this study, we analyzed
artificial microRNAs (amiRs) delivered by self-complementary adeno-associated
virus (scAAV) vectors for treatment of hAd5 infections in immunosuppressed
Syrian hamsters. In vitro evaluation of amiRs targeting the E1A, pTP, IVa2,
and hexon genes of hAd5 revealed that two scAAV vectors containing three
copies of amiR-pTP and three copies of amiR-E1A, or six copies of amiR-pTP,
efficiently inhibited hAd5 replication and improved the viability of
hAd5-infected cells. Prophylactic application of amiR-pTP/amiR-E1A- and amiR-
pTP-expressing scAAV9 vectors, respectively, to immunosuppressed Syrian
hamsters resulted in the reduction of hAd5 levels in the liver of up to two
orders of magnitude and in reduction of liver damage. Concomitant application
of the vectors also resulted in a decrease of hepatic hAd5 infection. No side
effects were observed. These data demonstrate anti-adenoviral RNAi as a
promising new approach to combat hAd5 infection.
en
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
adenovirus infection
dc.subject
RNA interference
dc.subject
antiviral therapy
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie
dc.title
Anti-adenoviral Artificial MicroRNAs Expressed from AAV9 Vectors Inhibit Human
Adenovirus Infection in Immunosuppressed Syrian Hamsters
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Molecular Therapy - Nucleic Acids. - 8 (2017), S. 300-316
dcterms.bibliographicCitation.doi
10.1016/j.omtn.2017.07.002
dcterms.bibliographicCitation.url
http://doi.org/10.1016/j.omtn.2017.07.002
refubium.affiliation
Veterinärmedizin
de
refubium.mycore.fudocsId
FUDOCS_document_000000027980
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008755
dcterms.accessRights.openaire
open access