2007
DOI: 10.1038/sj.gt.3303011
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Inhibition of HIV-1 replication with designed miRNAs expressed from RNA polymerase II promoters

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Cited by 27 publications
(21 citation statements)
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“…While many RNAi knockdown vectors designed for general laboratory experimentation use short-hairpin designs, overexpression of shRNAs using RNA polymerase III vectors have been demonstrated to mediate toxicity via saturation of microRNA processing pathways leading to lethality in animal models [35,36]. These shRNA vectors have also been shown to be toxic to transduced human T cells [37] and we also observed this phenomenon in preliminary experiments.…”
Section: Discussionsupporting
confidence: 54%
“…While many RNAi knockdown vectors designed for general laboratory experimentation use short-hairpin designs, overexpression of shRNAs using RNA polymerase III vectors have been demonstrated to mediate toxicity via saturation of microRNA processing pathways leading to lethality in animal models [35,36]. These shRNA vectors have also been shown to be toxic to transduced human T cells [37] and we also observed this phenomenon in preliminary experiments.…”
Section: Discussionsupporting
confidence: 54%
“…Few target genes that are regulated by microRNAs are currently documented, but the ones identified have important roles in apoptosis, homeobox regulation, development [30,[97][98][99][100][101], cell growth and apoptosis [13,14], viral infection [15,19], and human cancer [81,[102][103][104]. This type of gene control represents a new regulatory mechanism and is predicted to affect many crucial cellular processes, including developmental programs.…”
Section: Microrna Regulation Mechanisms and Target Predictionmentioning
confidence: 99%
“…Various types of small, noncoding RNAs exist as modulators of gene expression, affecting transcription rate, mRNA stability, and mRNA translation into functional proteins. What was once believed to be a specialized function occurring only in plants [8,9] or worms [1,10] has now been shown to control regulatory pathways in several mammalian biological processes, such as cell growth and apoptosis [11][12][13][14], viral infection [15][16][17][18][19], neural function [20 -23], and stem cell function [21, 24 -37]. Here, we outline the issues related to microRNA expression profiling in MSC as an example of how these studies are useful for classifying differentiating cells and, potentially, understanding molecular networks active during differentiation.…”
Section: Introductionmentioning
confidence: 99%
“…22 However, we and others recognized that a high level of sustained shRNA expression may be toxic to cells because of competition with endogenous micro-RNA biogenesis, induction of interferon responses, and/or off-targeting effects. 23,[26][27][28][29][30][31][32][33] To stably reduce CCR5 expression without cytotoxicity, we identified a highly efficient shRNA (shRNA 1005) directed to human CCR5 mRNA using the enzymatic production of RNAi libraries (EPRIL) screening technique. 21,34 We expressed shRNA 1005 using the transcriptionally weak H1 promoter to stably reduce CCR5 expression without inducing cytotoxicity in human primary peripheral blood lymphocytes in vitro.…”
Section: Introductionmentioning
confidence: 99%