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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Book ChapterDOI
Identifying Genetic Dependencies in Cancer by Analyzing siRNA Screens in Tumor Cell Line Panels.
TL;DR: A computational protocol for analyzing loss-of-function screens to identify genetic dependencies associated with particular molecular features and the steps required to process the siRNA screen data, integrate the results with genotypic information, and finally the integration of protein-protein interaction data to interpret these dependencies are described.
Book ChapterDOI
Multiple genetic manipulations of DT40 cell line
Akira Motegi,Minoru Takata +1 more
TL;DR: This chapter describes the current standard methods of multiple genetic manipulation in DT40 cells, with a particular emphasis on describing the basic concepts and theoretical background of the genetic manipulation ofDT40 cells for researchers who are new to such techniques.
Dissertation
Pathophysiological relevance of PDE inhibition in lung fibroblasts for the treatment of pulmonary diseases
TL;DR: Das Glück, kein Reiter wird's erjagen, es ist nicht dort und nicht hier, und ungeahnt erblüht es dir.
Journal ArticleDOI
Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering
Sandra Hinkelmann,Alexandra H Springwald,Sabine Schulze,Ute Hempel,F. Mitrach,Christian Wölk,Michael C. Hacker,Michaela Schulz-Siegmund +7 more
TL;DR: The results suggest osteoanabolic effects of pre-differentiated and chordin-silenced microtissues on bone homeostasis and enhanced ALP activity and osteoprotegerin (OPG) secretion in the model system compared to control microtissue.
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.