Journalartikel
Autorenliste: Stieger, Knut; Schroeder, Josef; Provost, Nathalie; Mendes-Madeira, Alexandra; Belbellaa, Brahim; Le Meur, Guylene; Weber, Michel; Deschamps, Jack-Yves; Lorenz, Birgit; Moullier, Philippe; Rolling, Fabienne
Jahr der Veröffentlichung: 2009
Seiten: 516-523
Zeitschrift: Molecular Therapy
Bandnummer: 17
Heftnummer: 3
ISSN: 1525-0016
eISSN: 1525-0024
Open Access Status: Hybrid
DOI Link: https://doi.org/10.1038/mt.2008.283
Verlag: Cell Press
Abstract:
Gene transfer to the retina using recombinant adeno-associated viral (rAAV) vectors has proven to be an effective option for the treatment of retinal degenerative diseases in several animal models and has recently advanced into clinical trials in humans. To date, intracellular trafficking of AAV vectors and subsequent capsid degradation has been studied only in vitro, but the fate of AAV particles in transduced cells following subretinal injection has yet to be elucidated. Using electron microscopy and western blot, we analyzed retinas of one primate and four dogs that had been subretinally injected with AAV2/4, -2/5, or -2/2 serotypes and that displayed efficient gene transfer over several years. We show that intact AAV particles are still present in retinal cells, for up to 6 years after successful gene transfer in these large animals. The persistence of intact vector particles in the target organ, several years postadministration, is totally unexpected and, therefore, represents a new and unanticipated safety issue to consider at a time when gene therapy clinical trials raise new immunological concerns.
Zitierstile
Harvard-Zitierstil: Stieger, K., Schroeder, J., Provost, N., Mendes-Madeira, A., Belbellaa, B., Le Meur, G., et al. (2009) Detection of Intact rAAV Particles up to 6 Years After Successful Gene Transfer in the Retina of Dogs and Primates, Molecular Therapy, 17(3), pp. 516-523. https://doi.org/10.1038/mt.2008.283
APA-Zitierstil: Stieger, K., Schroeder, J., Provost, N., Mendes-Madeira, A., Belbellaa, B., Le Meur, G., Weber, M., Deschamps, J., Lorenz, B., Moullier, P., & Rolling, F. (2009). Detection of Intact rAAV Particles up to 6 Years After Successful Gene Transfer in the Retina of Dogs and Primates. Molecular Therapy. 17(3), 516-523. https://doi.org/10.1038/mt.2008.283
Schlagwörter
ADENOASSOCIATED VIRUS TYPE-2; AIRWAY EPITHELIA; GROWTH-FACTOR RECEPTOR; INTRACELLULAR TRAFFICKING; LEBERS CONGENITAL AMAUROSIS; NUCLEAR TRAFFICKING; PIGMENTED EPITHELIUM; Subretinal injection; TRANSDUCTION EFFICIENCY
