475. In Vivo Targeting of MLV(HIV) Pseudotype Vectors to T Lymphocytes in a Transgenic Mouse Model
| Autor: | Ulrich Kalinke, Matthias Schweizer, Klaus Cichutek, Sylvia Raupp, Silke Schuele, Stefanie Steidl, Cheick Coulibaly |
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| Rok vydání: | 2005 |
| Předmět: |
Pharmacology
education.field_of_study biology viruses Transgene Population virus diseases biology.organism_classification Virology Molecular biology Transduction (genetics) In vivo Drug Discovery Murine leukemia virus Genetics Pseudotyping Molecular Medicine education Molecular Biology Tropism Ex vivo |
| Zdroj: | Molecular Therapy. 11:S184-S185 |
| ISSN: | 1525-0016 |
| Popis: | Top of pageAbstract Retroviral vectors derived from murine leukemia virus (MLV) and pseudotyped with the HIV-1 envelope (Env) protein enable specific gene transfer into CD4+ cells and may therefore be suitable for in vivo gene transfer for the treatment of various inherited or acquired disorders involving T cells including severe combined immunodeficiency disease (SCID), AIDS or T cell lymphoma. In cell culture, MLV(HIV) vectors are not only specific for CD4, but also for HIV coreceptors CCR5 or CXCR4, depending on the particular HIV Env protein used for pseudotyping. Here we tested the in vivo distribution of a CD4/CCR5-specific MLV(HIV) pseudotype vector transferring the EGFP gene in a transgenic mouse strain expressing human CD4 and CCR5 under control of the murine CD4 promoter. At first, gene transfer specificity was demonstrated by ex vivo transduction of a mixed population of spleen lymphocytes. Only cells from double transgenic CD4+/CCR5+ mice were transduced by CD4/CCR5-tropic vectors, whereas gene transfer into lymphocytes from single transgenic CD4+or CCR5+ mice or double transgenic CD4+/CXCR4+ mice was not detectable. Subsequently, MLV(HIV) vectors were administered intravenously or intraperitoneally, and various tissues were analyzed for successful vector transfer. EGFP expression and vector sequences could be detected exclusively in lymphocytes from CD4+/CCR5+ mice, but neither in CD4+/CXCR4+mice nor in single transgenic CD4+, CXCR4, or CCR5+mice. In contrast, when using MLV control vectors pseudotyped with VSV-G, EGFP-expressing lymphocytes were readily detected in mice of all genotypes described.In summary, the suitability of MLV(HIV) vector particles for in vivo gene transfer and their specific tropism for CD4+/CCR5+ lymphocytes was demonstrated. |
| Databáze: | OpenAIRE |
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