2008
DOI: 10.1038/sj.mt.6300411
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Physiological Promoters Reduce the Genotoxic Risk of Integrating Gene Vectors

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Cited by 91 publications
(148 citation statements)
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References 33 publications
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“…A retroviral transactivation assay could show that the internal SFFV but not PGK or EF1a promoter was able to enhance expression from a distantly located mCMV promoter. 50 In line with these results, we could show that the SFFV promoter was also capable of efficiently activating the mCMV in a bidirectional setting. This also applied to the PGK and the CD3 promoters supporting the hypothesis that the activation of a neighboring promoter depends on enhancer strength and distance.…”
Section: Discussionsupporting
confidence: 79%
“…A retroviral transactivation assay could show that the internal SFFV but not PGK or EF1a promoter was able to enhance expression from a distantly located mCMV promoter. 50 In line with these results, we could show that the SFFV promoter was also capable of efficiently activating the mCMV in a bidirectional setting. This also applied to the PGK and the CD3 promoters supporting the hypothesis that the activation of a neighboring promoter depends on enhancer strength and distance.…”
Section: Discussionsupporting
confidence: 79%
“…9 Such a cellular internal promoter is not only more physiological but also should minimize the risk of insertional mutagenesis as described with the use of cellular promoters. 22 In the specific context of the WAS LV, we show that the WPRE is required to obtain an adequate expression of the WAS transgene, although it does not seem to be required for the production of high viral titer. We also show that either of the mutant tested can be used to replace the native WPRE to express equivalent levels of transgene.…”
Section: Discussionmentioning
confidence: 84%
“…Extensive studies have shown that the enhancer sequences are the major cause of cell transformation, making the design of viral vectors for life-long therapy approaches even more challenging. [8][9][10] Insulators mark the boundaries of chromatin domains and limit the range of action of enhancers and silencers. 11 They are characterized by at least one of the following properties: Enhancer blocking and/or boundary.…”
Section: Introductionmentioning
confidence: 99%
“…18,23,24 A shorter sub-portion of the cHS4, namely the 250-bp insulator core element, is more suitable with viral vectors' biology, but it failed to reproduce the activity of the full-length element. 9,20,25,26 The enhancer-blocking function of the cHS4 has been attributed to the CCCTC-binding factor (CTCF), an 11-zinc-finger DNA-binding protein highly conserved in vertebrates. CTCF was implicated in diverse regulatory functions, including transcriptional activation/ repression, insulation and imprinting.…”
Section: Introductionmentioning
confidence: 99%