Effective gene therapy with nonintegrating lentiviral vectors
| Autor: | John R. Heckenlively, Christine Kinnon, Steven J. Howe, Manfred Schmidt, Robin R. Ali, Alexander J. Smith, Adrian J. Thrasher, Kamaljit S. Balaggan, S. E. Barker, Rafael J. Yáñez-Muñoz, CC Bartholomae, A MacNeil, Yanai Duran, Christof von Kalle, Prateek K. Buch, Robert E MacLaren, Patrick N. Anderson |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
cis-trans-Isomerases
Genetic enhancement Transgene Virus Integration Genetic Vectors Green Fluorescent Proteins Computational biology Biology General Biochemistry Genetics and Molecular Biology Retina Viral vector Insertional mutagenesis Mice In vivo Electroretinography Tumor Cells Cultured Animals Humans Eye Proteins Pigment Epithelium of Eye Lentivirus Brain General Medicine Genetic Therapy biology.organism_classification Virology Rats Cis-trans-Isomerases Female Carrier Proteins HeLa Cells |
| Zdroj: | Nature medicine. 12(3) |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Retroviral and lentiviral vector integration into host-cell chromosomes carries with it a finite chance of causing insertional mutagenesis1. 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 transduction4,5,6. 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. |
| Databáze: | OpenAIRE |
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