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| Content Provider | Springer Nature Link |
|---|---|
| Author | Bellodi Privato, Marta Meur, Guylène Aubert, Dominique Mendes Madera, Alexandra Pichard, Virginie Rolling, Fabienne Ferry, Nicolas |
| Copyright Year | 2004 |
| Abstract | Gene therapy of inherited hepatic disease relies on sustained expression of the therapeutic transgene. In many instances, such expression will require immune tolerization to the non-self therapeutic transgene product. We previously demonstrated that a cytotoxic immune response eliminated hepatocytes after in vivo transduction using recombinant retroviral vectors. In the present study we investigated whether prior gene transfer to the retina, which is suspected to induce immune tolerance, could alleviate the immune response occurring after retrovirus mediated gene transfer to the liver. Retinal cells were transduced using adeno-associated viral vectors harbouring a β-galactosidase transgene. Sixty days later, regenerating hepatocytes were transduced after partial hepatectomy using a recombinant retrovirus carrying the transgene. Three weeks later, anti β-galactosidase antibodies were present in all animals. Elimination of the transduced hepatocytes eventually occurred in all animals by 2 months after liver gene transfer, although sustained β-galactosidase expression was still present in the retina in 66% of the animals. We conclude that although the retina behaves as an immunoprivileged site, gene expression in the subretinal space is not sufficient to induce immune tolerance to a transgene product expressed in the liver. |
| Starting Page | 403 |
| Ending Page | 410 |
| Page Count | 8 |
| File Format | |
| ISSN | 09462716 |
| Journal | Journal of Molecular Medicine |
| Volume Number | 82 |
| Issue Number | 6 |
| e-ISSN | 14321440 |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2004-03-24 |
| Publisher Place | Berlin/Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Retrovirus Adeno-associated virus Retina Liver Gene therapy Immune response |
| Content Type | Text |
| Resource Type | Article |
| Subject | Drug Discovery Molecular Medicine Genetics (clinical) |
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