Effective gene therapy with nonintegrating lentiviral vectors.
Retroviral and lentiviral vector integration into host-cell chromosomes carries with it a finite chance of causing insertional mutagenesis. This risk has been highlighted by the induction of malignancy in mouse models, and development of lymphoproliferative disease in three individuals with severe c...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2006
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| _version_ | 1797083604556185600 |
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| author | Yáñez-Muñoz, R Balaggan, K MacNeil, A Howe, S Schmidt, M Smith, A Buch, P Maclaren, R Anderson, P Barker, SE Duran, Y Bartholomae, C von Kalle, C Heckenlively, JR Kinnon, C Ali, R Thrasher, A |
| author_facet | Yáñez-Muñoz, R Balaggan, K MacNeil, A Howe, S Schmidt, M Smith, A Buch, P Maclaren, R Anderson, P Barker, SE Duran, Y Bartholomae, C von Kalle, C Heckenlively, JR Kinnon, C Ali, R Thrasher, A |
| author_sort | Yáñez-Muñoz, R |
| collection | OXFORD |
| description | Retroviral and lentiviral vector integration into host-cell chromosomes carries with it a finite chance of causing insertional mutagenesis. This risk has been highlighted by the induction of malignancy in mouse models, and development of lymphoproliferative disease in three individuals with severe combined immunodeficiency-X1 (refs. 2,3). Therefore, a key challenge for clinical therapies based on retroviral vectors is to achieve stable transgene expression while minimizing insertional mutagenesis. Recent in vitro studies have shown that integration-deficient lentiviral vectors can mediate stable transduction. With similar vectors, we now show efficient and sustained transgene expression in vivo in rodent ocular and brain tissues. We also show substantial rescue of clinically relevant rodent models of retinal degeneration. Therefore, the high efficiency of gene transfer and expression mediated by lentiviruses can be harnessed in vivo without a requirement for vector integration. For therapeutic application to postmitotic tissues, this system substantially reduces the risk of insertional mutagenesis. |
| first_indexed | 2024-03-07T01:43:45Z |
| format | Journal article |
| id | oxford-uuid:97b5d90e-6a7b-4a99-8c9f-c78530b5bc66 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:43:45Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:97b5d90e-6a7b-4a99-8c9f-c78530b5bc662022-03-27T00:02:01ZEffective gene therapy with nonintegrating lentiviral vectors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:97b5d90e-6a7b-4a99-8c9f-c78530b5bc66EnglishSymplectic Elements at Oxford2006Yáñez-Muñoz, RBalaggan, KMacNeil, AHowe, SSchmidt, MSmith, ABuch, PMaclaren, RAnderson, PBarker, SEDuran, YBartholomae, Cvon Kalle, CHeckenlively, JRKinnon, CAli, RThrasher, ARetroviral and lentiviral vector integration into host-cell chromosomes carries with it a finite chance of causing insertional mutagenesis. This risk has been highlighted by the induction of malignancy in mouse models, and development of lymphoproliferative disease in three individuals with severe combined immunodeficiency-X1 (refs. 2,3). Therefore, a key challenge for clinical therapies based on retroviral vectors is to achieve stable transgene expression while minimizing insertional mutagenesis. Recent in vitro studies have shown that integration-deficient lentiviral vectors can mediate stable transduction. With similar vectors, we now show efficient and sustained transgene expression in vivo in rodent ocular and brain tissues. We also show substantial rescue of clinically relevant rodent models of retinal degeneration. Therefore, the high efficiency of gene transfer and expression mediated by lentiviruses can be harnessed in vivo without a requirement for vector integration. For therapeutic application to postmitotic tissues, this system substantially reduces the risk of insertional mutagenesis. |
| spellingShingle | Yáñez-Muñoz, R Balaggan, K MacNeil, A Howe, S Schmidt, M Smith, A Buch, P Maclaren, R Anderson, P Barker, SE Duran, Y Bartholomae, C von Kalle, C Heckenlively, JR Kinnon, C Ali, R Thrasher, A Effective gene therapy with nonintegrating lentiviral vectors. |
| title | Effective gene therapy with nonintegrating lentiviral vectors. |
| title_full | Effective gene therapy with nonintegrating lentiviral vectors. |
| title_fullStr | Effective gene therapy with nonintegrating lentiviral vectors. |
| title_full_unstemmed | Effective gene therapy with nonintegrating lentiviral vectors. |
| title_short | Effective gene therapy with nonintegrating lentiviral vectors. |
| title_sort | effective gene therapy with nonintegrating lentiviral vectors |
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