Gene therapy in the second eye of RPE65-deficient dogs improves retinal function
| Autor: | Paul G. Curran, Robin R. Ali, S. E. Barker, Matthew J. Annear, Alexander J. Smith, James W B Bainbridge, Simon M. Petersen-Jones, Joshua T. Bartoe |
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| Rok vydání: | 2010 |
| Předmět: |
cis-trans-Isomerases
Pathology medicine.medical_specialty genetic structures Eye disease Genetic enhancement Genetic Vectors Leber Congenital Amaurosis Biology Retina Article Viral vector Dogs Electroretinography Genetics medicine Animals Humans Eye Proteins Molecular Biology medicine.diagnostic_test Genetic Therapy Dependovirus medicine.disease eye diseases medicine.anatomical_structure Immunoglobulin M Immunoglobulin G Cis-trans-Isomerases Molecular Medicine sense organs Carrier Proteins Retinopathy |
| Zdroj: | Gene Therapy. 18:53-61 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/gt.2010.111 |
| Popis: | The purpose of this study was to evaluate whether immune responses interfered with gene therapy rescue using subretinally delivered recombinant adeno-associated viral vector serotype 2 carrying the RPE65 cDNA gene driven by the human RPE65 promoter (rAAV2.hRPE65p.hRPE65) in the second eye of RPE65−/− dogs that had previously been treated in a similar manner in the other eye. Bilateral subretinal injection was performed in nine dogs with the second eye treated 85–180 days after the first. Electroretinography (ERG) and vision testing showed rescue in 16 of 18 treated eyes, with no significant difference between first and second treated eyes. A serum neutralizing antibody (NAb) response to rAAV2 was detected in all treated animals, but this did not prevent or reduce the effectiveness of rescue in the second treated eye. We conclude that successful rescue using subretinal rAAV2.hRPE65p.hRPE65 gene therapy in the second eye is not precluded by prior gene therapy in the contralateral eye of the RPE65−/− dog. This finding has important implications for the treatment of human LCA type II patients. |
| Databáze: | OpenAIRE |
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