دورية أكاديمية
GP64-pseudotyped lentiviral vectors target liver endothelial cells and correct hemophilia A mice
| العنوان: | GP64-pseudotyped lentiviral vectors target liver endothelial cells and correct hemophilia A mice |
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| المؤلفون: | Michela Milani, Cesare Canepari, Simone Assanelli, Simone Merlin, Ester Borroni, Francesco Starinieri, Mauro Biffi, Fabio Russo, Anna Fabiano, Desirèe Zambroni, Andrea Annoni, Luigi Naldini, Antonia Follenzi, Alessio Cantore |
| المصدر: | EMBO Molecular Medicine, Vol 16, Iss 6, Pp 1427-1450 (2024) |
| بيانات النشر: | Springer Nature, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | In Vivo Gene Therapy, Lentiviral Vectors, Liver Endothelial Cells, Hemophilia A, Envelope Engineering, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract Lentiviral vectors (LV) are efficient vehicles for in vivo gene delivery to the liver. LV integration into the chromatin of target cells ensures their transmission upon proliferation, thus allowing potentially life-long gene therapy following a single administration, even to young individuals. The glycoprotein of the vesicular stomatitis virus (VSV.G) is widely used to pseudotype LV, as it confers broad tropism and high stability. The baculovirus-derived GP64 envelope protein has been proposed as an alternative for in vivo liver-directed gene therapy. Here, we perform a detailed comparison of VSV.G- and GP64-pseudotyped LV in vitro and in vivo. We report that VSV.G-LV transduced hepatocytes better than GP64-LV, however the latter showed improved transduction of liver sinusoidal endothelial cells (LSEC). Combining GP64-pseudotyping with the high surface content of the phagocytosis inhibitor CD47 further enhanced LSEC transduction. Coagulation factor VIII (FVIII), the gene mutated in hemophilia A, is naturally expressed by LSEC, thus we exploited GP64-LV to deliver a FVIII transgene under the control of the endogenous FVIII promoter and achieved therapeutic amounts of FVIII and correction of hemophilia A mice. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 |
| العلاقة: | https://doaj.org/toc/1757-4684Test |
| DOI: | 10.1038/s44321-024-00072-8 |
| الوصول الحر: | https://doaj.org/article/b045f6dbf8624a8e8e0b19badc7c0b7bTest |
| رقم الانضمام: | edsdoj.b045f6dbf8624a8e8e0b19badc7c0b7b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 |
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| DOI: | 10.1038/s44321-024-00072-8 |