Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Mattar, Citra Nurfarah Zaini [VerfasserIn]   i
 Gil-Fariña, Irene [VerfasserIn]   i
 Käppel, Christine [VerfasserIn]   i
 Schmidt, Manfred [VerfasserIn]   i
Titel:In utero transfer of adeno-associated viral vectors produces long-term factor IX levels in a cynomolgus macaque model
Verf.angabe:Citra N. Z. Mattar, Irene Gil-Farina, Cecilia Rosales, Nuryanti Johana, Yvonne Yi Wan Tan, Jenny McIntosh, Christine Kaeppel, Simon N. Waddington, Arijit Biswas, Mahesh Choolani, Manfred Schmidt, Amit C. Nathwani and Jerry K. Y. Chan
Jahr:2017
Umfang:11 S.
Fussnoten:Available online 24 April 2017 ; Gesehen am 12.06.2018
Titel Quelle:Enthalten in: Molecular therapy
Ort Quelle:Amsterdam : Elsevier, 2000
Jahr Quelle:2017
Band/Heft Quelle:25(2017), 8, Seite 1843-1853
ISSN Quelle:1525-0024
Abstract:The safe correction of an inherited bleeding disorder in utero prior to the onset of organ damage is highly desirable. Here, we report long-term transgene expression over more than 6 years without toxicity following a single intrauterine gene transfer (IUGT) at 0.9G using recombinant adeno-associated vector (AAV)-human factor IX (hFIX) in the non-human primate model we have previously described. Four of six treated animals monitored for around 74 months expressed hFIX at therapeutic levels (3.9%-120.0%). Long-term expression was 6-fold higher in males and with AAV8 compared to AAV5, mediated almost completely at this stage by random genome-wide hepatic proviral integrations, with no evidence of hotspots. Post-natal AAV challenge without immunosuppression was evaluated in two animals exhibiting chronic low transgene expression. The brief neutralizing immune reaction elicited had no adverse effect and, although expression was not improved at the dose administered, no clinical toxicity was observed. This long-term surveillance thus confirms the safety of late-gestation AAV-hFIX transfer and demonstrates that postnatal re-administration can be performed without immunosuppression, although it requires dose optimization for the desired expression. Nevertheless, eventual vector genotoxicity and the possibility of germline transmission will require lifelong monitoring and further evaluation of the reproductive function of treated animals.
DOI:doi:10.1016/j.ymthe.2017.04.003
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.

kostenfrei: Volltext: http://dx.doi.org/10.1016/j.ymthe.2017.04.003
 kostenfrei: Volltext: http://www.sciencedirect.com/science/article/pii/S1525001617301624
 DOI: https://doi.org/10.1016/j.ymthe.2017.04.003
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:adeno-associated viral vector
 immune tolerance
 intrauterine gene transfer
 long-term expression
 non-human primate
 non-responder
 vector integration
K10plus-PPN:1576265552
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68260347   QR-Code
zum Seitenanfang