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• W2027832851 abstract "Three RNA features have been identified that elevate retroviral transgene expression: an intron in the 5′ untranslated region (5′UTR), the absence of aberrant translational start codons and the presence of the post-transcriptional regulatory element (PRE) of the woodchuck hepatitis virus in the 3′UTR. To include such elements into self-inactivating (SIN) vectors with potentially improved safety, we excised the strong retroviral promoter from the U3 region of the 3′ long terminal repeat (LTR) and inserted it either downstream or upstream of the retroviral RNA packaging signal (Ψ). The latter concept is new and allows the use of an intron in the 5′UTR, taking advantage of retroviral splice sites surrounding Ψ. Three LTR and four SIN vectors were compared to address the impact of RNA elements on titer, splice regulation and transgene expression. Although titers of SIN vectors were about 20-fold lower than those of their LTR counterparts, inclusion of the PRE allowed production of more than 106 infectious units per ml without further vector optimizations. In comparison with state-of-the-art LTR vectors, the intron-containing SIN vectors showed greatly improved splicing. With regard to transgene expression, the intron-containing SIN vectors largely matched or even exceeded the LTR counterparts in all cell types investigated (embryonic carcinoma cells, fibroblasts, primary T cells and hematopoietic progenitor cells)." @default.
• W2027832851 created "2016-06-24" @default.
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• W2027832851 date "2004-09-16" @default.
• W2027832851 modified "2023-10-12" @default.
• W2027832851 title "Self-inactivating retroviral vectors with improved RNA processing" @default.
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• W2027832851 doi "https://doi.org/10.1038/sj.gt.3302309" @default.
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