دورية أكاديمية
Prednisolone reduces the interferon response to AAV in cynomolgus macaques and may increase liver gene expression
| العنوان: | Prednisolone reduces the interferon response to AAV in cynomolgus macaques and may increase liver gene expression |
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| المؤلفون: | Lili Wang, Claude C. Warzecha, Alexander Kistner, Jessica A. Chichester, Peter Bell, Elizabeth L. Buza, Zhenning He, M. Betina Pampena, Julien Couthouis, Sunjay Sethi, Kathleen McKeever, Michael R. Betts, Emil Kakkis, James M. Wilson, Samuel Wadsworth, Barbara A. Sullivan |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 24, Iss , Pp 292-305 (2022) |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Genetics LCC:Cytology |
| مصطلحات موضوعية: | adeno-associated virus, AAV8, ornithine transcarbamylase deficiency, non-human primates, sex, immunosuppression, Genetics, QH426-470, Cytology, QH573-671 |
| الوصف: | Ornithine transcarbamylase deficiency is a rare X-linked genetic urea cycle disorder leading to episodes of acute hyperammonemia, adverse cognitive and neurological effects, hospitalizations, and in some cases death. DTX301, a non-replicating, recombinant self-complimentary adeno-associated virus vector serotype 8 (scAAV8)-encoding human ornithine transcarbamylase, is a promising gene therapy for ornithine transcarbamylase deficiency; however, the impact of sex and prophylactic immunosuppression on ornithine transcarbamylase gene therapy outcomes is not well characterized. This study sought to describe the impact of sex and immunosuppression in adult, sexually mature female and male cynomolgus macaques through day 140 after DTX301 administration. Four study groups (n = 3/group) were included: male non-immunosuppressed; male immunosuppressed; female non-immunosuppressed; and female immunosuppressed. DTX301 was well tolerated with and without immunosuppression; no notable differences were observed between female and male groups across outcome measures. Prednisolone-treated animals exhibited a trend toward greater vector genome and transgene expression, although the differences were not statistically significant. The hepatic interferon gene signature was significantly decreased in prednisolone-treated animals, and a significant inverse relationship was observed between interferon gene signature levels and hepatic vector DNA and transgene RNA. These observations were not sustained upon immunosuppression withdrawal. Further studies may determine whether the observed effect can be prolonged. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2329-0501 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2329050122000080; https://doaj.org/toc/2329-0501 |
| DOI: | 10.1016/j.omtm.2022.01.007 |
| URL الوصول: | https://doaj.org/article/0bb545c351f24bafb56d6307da45c4b4 |
| رقم الأكسشن: | edsdoj.0bb545c351f24bafb56d6307da45c4b4 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23290501 |
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| DOI: | 10.1016/j.omtm.2022.01.007 |