Stieger, Knut and Schroeder, Josef and Provost, Nathalie and Mendes-Madeira, Alexandra and Belbellaa, Brahim and Le Meur, Guylene and Weber, Michel and Deschamps, Jack-Yves and Lorenz, Birgit and Moullier, Philippe and Rolling, Fabienne (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. ISSN 1525-0016, 1525-0024
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ADENOASSOCIATED VIRUS TYPE-2; LEBERS CONGENITAL AMAUROSIS; GROWTH-FACTOR RECEPTOR; AIRWAY EPITHELIA; INTRACELLULAR TRAFFICKING; TRANSDUCTION EFFICIENCY; PIGMENTED EPITHELIUM; SUBRETINAL INJECTION; NUCLEAR TRAFFICKING; ENDOTHELIAL-CELLS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Oct 2020 06:35 |
| Last Modified: | 05 Oct 2020 06:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29419 |
Actions (login required)
 |
View Item |
