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• W1993965384 abstract "Recent published data have shown the efficacy of gene therapy treatments of certain monogenic diseases. Risks of insertional oncogenesis, however, indicate the necessity of developing new vectors with weaker or cell-restricted promoters to minimize the <i>trans</i>-activation activity of integrated proviruses. We have inserted the proximal promoter of the <i>vav</i> proto-oncogene into self-inactivating lentiviral vectors (vav-LVs) and investigated the expression pattern and therapeutic efficacy of these vectors. Compared with other LVs frequently used in gene therapy, vav-LVs mediated a weak, though homogeneous and stable, expression in <i>in vitro</i>–cultured cells. Transplantation experiments using transduced mouse bone marrow and human CD34⁺ cells confirmed the stable activity of the promoter <i>in vivo</i>. To investigate whether the weak activity of this promoter was compatible with a therapeutic effect, a LV expressing the Fanconi anemia A (<i>FANCA</i>) gene was constructed (vav-FANCA LV). Although this vector induced a low expression of <i>FANCA</i>, compared to the expression induced by a LV harboring the spleen focus-forming virus (SFFV) promoter, the two vectors corrected the phenotype of cells from a patient with FA-A with the same efficacy. We propose that self-inactivating vectors harboring weak promoters, such as the <i>vav</i> promoter, will improve the safety of gene therapy and will be of particular interest for the treatment of diseases where a high expression of the transgene is not required." @default.
• W1993965384 created "2016-06-24" @default.
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• W1993965384 date "2007-08-01" @default.
• W1993965384 modified "2023-09-27" @default.
• W1993965384 title "Characteristics of Lentiviral Vectors Harboring the Proximal Promoter of the vav Proto-oncogene: A Weak and Efficient Promoter for Gene Therapy" @default.
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• W1993965384 doi "https://doi.org/10.1038/sj.mt.6300213" @default.
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