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
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Advances in siRNA delivery strategies for the treatment of MDR cancer.
TL;DR: In this paper, the authors investigated the potential for efficient delivery of siRNA to MDR cancer cells using nanocarrier functionalization, cancer immunotherapy and cancer targeting, and found that the barriers impeding siRNA therapeutics delivery and impacting the treatment outcome must overcome with negligible systemic toxicity.
Journal ArticleDOI
Downregulation of c-Myc is involved in TLR3-mediated tumor death of neuroblastoma xenografts
Li Ling Lin,Chao-Cheng Huang,Chao-Cheng Huang,Chia-Ling Wu,Min-Tsui Wu,Wen-Ming Hsu,Jiin-Haur Chuang +6 more
TL;DR: It is suggested that c-Myc overexpression may increase sensitivity to poly(I:C)-induced tumor growth arrest and ROS-mediated apoptosis in NB, and future treatment recommendations are provided.
Journal ArticleDOI
CRISPR guides induce gene silencing in plants in the absence of Cas
Veerendra Kumar Sharma,Sandeep R. Marla,Weng-Hui Zheng,Divya Mishra,Jun Huang,Wei Zhang,Geoffrey P. Morris,David Cook +7 more
TL;DR: In this paper , the use of CRISPR-Cas13 in plants to reduce both viral and endogenous RNA was reported, and it was shown that crRNA designed to guide Cas13 could, in the absence of the Cas13 protein, cause substantial reduction in RNA levels.
Journal ArticleDOI
Functional inhibition of chemokine receptor CCR2 by dicer-substrate-siRNA prevents pain development.
Valérie Bégin-Lavallée,Élora Midavaine,Marc-André Dansereau,Pascal Tétreault,Jean-Michel Longpré,Ashley M. Jacobi,Scott D. Rose,Mark A. Behlke,Nicolas Beaudet,Philippe Sarret +9 more
TL;DR: These results validate CCR2 as a an appropriate molecular target for pain control and demonstrate that RNAi-based gene therapy represent an highly specific alternative to classical pharmacological approaches to treat central pathologies such as chronic pain.
Journal ArticleDOI
From RNAi Screens to Molecular Function in Embryonic Stem Cells
TL;DR: A perspective on how to streamline the molecular characterization following the initial phenotypic description utilizing bacterial artificial chromosome (BAC) transgenesis is provided.
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.