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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Recent Advances in RNA Interference Therapeutics for CNS Diseases
TL;DR: Recent progress on RNA interference-based therapies in various model systems is reviewed and outstanding questions or concerns that have emerged as a result of an improved (and ever advancing) understanding of the technologies employed are highlighted.
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Applications of RNA interference in the treatment of arthritis.
Muhammad Farooq Rai,Hua Pan,Huimin Yan,Linda J. Sandell,Christine T. N. Pham,Samuel A. Wickline +5 more
TL;DR: A self-assembling peptide-based nanostructure is discussed that demonstrates the potential of overcoming many of the critical barriers preventing the translation of this technology to the clinic.
Journal ArticleDOI
Cancer-targeting siRNA delivery from porous silicon nanoparticles.
TL;DR: In this article, small interfering RNA (siRNA) loading into the pores of pSiNPs can protect siRNA from degradation as well as improve the cellular uptake, and the authors aimed to deliver MRP1 siRNA loaded into pSiNs to glioblastoma cells, and demonstrate downregulation of MRP 1 at the mRNA and protein levels.
Journal ArticleDOI
CRISPR Genome Engineering for Human Pluripotent Stem Cell Research.
TL;DR: The opportunities and the challenges of repurposing bacterial nucleases for genome editing are discussed, while appreciating their roles, primarily at the epigenomic granularity, while highlighting the major challenges that need to be met prior to bench-to-bedside translation.
Journal ArticleDOI
Microbial linguistics: perspectives and applications of microbial cell-to-cell communication
TL;DR: This review gives focus to the engineering principles necessary for rewiring bacterial chemo-communication for various applications, ranging from population-level gene expression control to the study of host-pathogen interactions.
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.