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• W2077307718 endingPage "615" @default.
• W2077307718 startingPage "603" @default.
• W2077307718 abstract "Retroviral vectors possess many advantages for use in gene therapy protocols, especially within the haematopoietic system. A number of attendant problems, however, still limit their safety in clinical application. The effects of the enhancer present in the retroviral long terminal repeat (LTR) are a major concern for the clinical usage of such vectors, as they can exert a powerful regulatory influence on the genes that surround them.To improve the safety and widen the applicability of retroviral vectors for use in gene therapy we have developed an enhancer-deleted (Delta-LTR) retroviral vector that retained high titre and demonstrated transcriptional activity in myeloid cells.When used to correct a mouse model of autosomal recessive chronic granulomatous disease, the Delta-LTR vectors gave acceptable levels of gene transfer to mouse bone marrow cells. Evidence for a slight preferential expression in myeloid cells was obtained with all the vectors studied. Nitroblue tetrazolium assay of superoxide generation in mouse bone marrow derived haematopoietic colonies revealed that transduction with Delta-LTR vectors could restore functional NADPH oxidase to cells from these animals. Superoxide assay of peripheral blood confirmed that, although relatively low numbers of cells were transduced, the Delta-LTR vector was capable of reconstituting very high levels of oxidase activity, comparable to that obtained from normal cells.The Delta-LTR vector described here could provide the basis for a new generation of retroviral vectors with improved safety." @default.
• W2077307718 created "2016-06-24" @default.
• W2077307718 creator A5001146963 @default.
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• W2077307718 date "2004-03-08" @default.
• W2077307718 modified "2023-10-10" @default.
• W2077307718 title "Enhancer-deleted retroviral vectors restore high levels of superoxide generation in a mouse model of CGD" @default.
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• W2077307718 doi "https://doi.org/10.1002/jgm.557" @default.
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