Journal ArticleDOI
Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application.
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TLDR
The types of off-target effects of siRNAs and methods to mitigate them are described to help enable effective application of this exciting technology.Abstract:
Small interfering RNAs (siRNAs) are widely used to study gene function owing to the ease with which they silence target genes, and there is considerable interest in their potential for therapeutic applications. In a remarkably short time since their discovery, siRNAs have entered human clinical trials in various disease areas. However, rapid acceptance of the use of siRNAs has been accompanied by recognition of several hurdles for the technology, including a lack of specificity. Off-target activity can complicate the interpretation of phenotypic effects in gene-silencing experiments and can potentially lead to unwanted toxicities. Here, we describe the types of off-target effects of siRNAs and methods to mitigate them, to help enable effective application of this exciting technology.read more
Citations
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EPAS1 resistance to miRNA-based regulation contributes to prolonged expression of HIF-2 during hypoxia in human endothelial cells.
TL;DR: In this article , the authors tested 23 microRNAs that were predicted to interact with the EPAS1 transcript (18 of which were induced during prolonged hypoxia), and demonstrated that none of them were functional in vitro.
Journal ArticleDOI
Discovery of Influenza A Virus Sequence Pairs and Their Combinations for Simultaneous Heterosubtypic Targeting that Hedge against Antiviral Resistance.
Keng Boon Wee,Raphael T.C. Lee,Jing Lin,Zacharias A.D. Pramono,Sebastian Maurer-Stroh,Sebastian Maurer-Stroh,Sebastian Maurer-Stroh +6 more
TL;DR: The identity of target sequence pairs for heterosubtypic targeting and their combinations for hedging antiviral resistance are useful toolkits to construct target graphs for different therapeutic objectives.
Dissertation
High-throughput siRNA Screen in Dendritic Cells to Discover New Genes Regulating Immunologic Tolerance
TL;DR: A high-throughput siRNA screen in bone marrow-derived DCs is developed and it is shown that BMDC expression of CD80, CD86, MHC II, and IL-12/23-p40 can identify candidate genes that regulate DC activation.
Journal ArticleDOI
Applications of CRISPR-Cas Technologies to Proteomics.
TL;DR: In this paper, the authors provide an introduction to the CRISPR-Cas technologies and demonstrate how they can be applied to solving proteome-centric questions in the context of proteomics.
Journal ArticleDOI
CRISPR system for genome engineering: the application for autophagy study.
TL;DR: The history, types and structure, the mechanism of action, the application of this powerful tool in autophagy research is evaluated and paves a bright future not only in research but also in medicine and biotechnology.
References
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Journal ArticleDOI
MicroRNAs: Target Recognition and Regulatory Functions
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.
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Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
TL;DR: 21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics.
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Prediction of Mammalian MicroRNA Targets
TL;DR: The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
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The nuclear RNase III Drosha initiates microRNA processing
Yoontae Lee,Chiyoung Ahn,Jinju Han,Hyounjeong Choi,Jaekwang Kim,Jeongbin Yim,Junho Lee,Patrick Provost,Olof Rådmark,Sun-Young Kim,V. Narry Kim +10 more
TL;DR: The two RNase III proteins, Drosha and Dicer, may collaborate in the stepwise processing of miRNAs, and have key roles in miRNA-mediated gene regulation in processes such as development and differentiation.
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Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs
Lee P. Lim,Nelson C. Lau,Philip W. Garrett-engele,Andrew Grimson,Janell M. Schelter,John C. Castle,David P. Bartel,Peter S. Linsley,Jason M. Johnson +8 more
TL;DR: These results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts, and seem to downregulate a far greater number of targets than previously appreciated.