Liver-directed lentiviral gene therapy in a dog model of hemophilia B
We investigated the efficacy of liver-directed gene therapy using lentiviral vectors in a large animal model of hemophilia B and evaluated the risk of insertional mutagenesis in tumor-prone mouse models. We showed that gene therapy using lentiviral vectors targeting the expression of a canine factor...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
4 March 2015
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| In: |
Science translational medicine
Year: 2015, Volume: 7, Issue: 277 |
| ISSN: | 1946-6242 |
| DOI: | 10.1126/scitranslmed.aaa1405 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1126/scitranslmed.aaa1405 Verlag, Volltext: http://stm.sciencemag.org/content/7/277/277ra28 
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| Author Notes: | Alessio Cantore, Marco Ranzani, Cynthia C. Bartholomae, Monica Volpin, Patrizia Della Valle, Francesca Sanvito, Lucia Sergi Sergi, Pierangela Gallina, Fabrizio Benedicenti, Dwight Bellinger, Robin Raymer, Elizabeth Merricks, Francesca Bellintani, Samia Martin, Claudio Doglioni, Armando D’Angelo, Thierry VandenDriessche, Marinee K. Chuah, Manfred Schmidt, Timothy Nichols, Eugenio Montini, Luigi Naldini |
| Summary: | We investigated the efficacy of liver-directed gene therapy using lentiviral vectors in a large animal model of hemophilia B and evaluated the risk of insertional mutagenesis in tumor-prone mouse models. We showed that gene therapy using lentiviral vectors targeting the expression of a canine factor IX transgene in hepatocytes was well tolerated and provided a stable long-term production of coagulation factor IX in dogs with hemophilia B. By exploiting three different mouse models designed to amplify the consequences of insertional mutagenesis, we showed that no genotoxicity was detected with these lentiviral vectors. Our findings suggest that lentiviral vectors may be an attractive candidate for gene therapy targeted to the liver and may be potentially useful for the treatment of hemophilia. Gene therapy with lentiviral vectors targeting transgene expression to hepatocytes provides stable reconstitution of clotting activity in dogs with hemophilia B and does not show genotoxicity in tumor-prone mice. Gene therapy with lentiviral vectors targeting transgene expression to hepatocytes provides stable reconstitution of clotting activity in dogs with hemophilia B and does not show genotoxicity in tumor-prone mice. |
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| Item Description: | Gesehen am 20.09.2017 |
| Physical Description: | Online Resource |
| ISSN: | 1946-6242 |
| DOI: | 10.1126/scitranslmed.aaa1405 |