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Journal ArticleDOI

Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application.

Aimee L. Jackson, +1 more
- 01 Jan 2010 - 
- Vol. 9, Iss: 1, pp 57-67
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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.

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Citations
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Genome editing in cotton: challenges and opportunities

TL;DR: In this paper , the authors highlighted the research opportunities for using the CRISPR/Cas system to address biotic and abiotic stresses, fibre quality, plant architecture and blooming, epigenetic changes, and gene stacking for commercially significant traits.
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Functional Antibody Delivery: Advances in Cellular Manipulation.

TL;DR: In this article , the authors focus on the emerging field of functional antibody delivery, which enables various cellular responses and cell manipulation, and present a review of the current state-of-the-art.
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HSP90β promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling

TL;DR: It is shown that Hsp90β exerted paralogue-specific role in osteoclastogenesis, and is a promising druggable target for the treatment of osteoporosis.
Posted ContentDOI

A comprehensive computational investigation into the conserved virulent proteins of Shigella sp unveils potential siRNA candidates as a new therapeutic strategy against shigellosis

TL;DR: In this article, a total of 241 conserved sequences from a 15 different conserved virulence genes of Shigella sp and through extensive rational validation using a plethora of computational algorithms; they primarily obtained fifty eight small interfering RNA (siRNA) candidates.
Journal ArticleDOI

A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis

TL;DR: Although the findings of this study require further wet-lab validation and optimization for therapeutic use in the treatment of shigellosis, the computationally validated siRNA candidates are expected to suppress the expression of the virulence genes, namely: IpgD and OspB and thus act as a prospective tool in the RNA interference (RNAi) pathway.
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

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

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.
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