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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Dissertation
Effects of siRNA-squalene nanoparticles on RET/PTCs junction oncogenes in papillary thyroid carcinoma : from molecular and cellular studies to preclinical investigations
TL;DR: The nanoparticles of siRNAs-SQ NPs were found to drastically reduce the tumor growth and RET/PTCs oncogene and oncoprotein expressions and highly support the use of siRNA-Sq NPs as a treatment for patients affected by PTC expressing RET/ PTCs.
Journal ArticleDOI
Cheminformatics Modeling of Gene Silencing for Both Natural and Chemically Modified siRNAs
Xialan Dong,Weifan Zheng +1 more
TL;DR: A new approach is proposed that can predict the potency of gene silencing by cm-siRNAs, which characterizes each nucleotide (NT) using 12 BCUT cheminformatics descriptors describing its charge distribution, hydrophobic and polar properties.
Posted ContentDOI
Chemically synthesized guide RNAs can direct CRISPR-CasRx cleavage of circRNAs with high efficiency and specificity
TL;DR: It is demonstrated that CRISPR/RfxCas13d (CasRx)-mediated circRNA depletion is, for the circRNAs studied, more efficient than Argonaute 2-dependent short hairpin RNA (agoshRNA)-mediated depletion and with fewer off-target effects on the linear host RNAs.
Posted ContentDOI
Structural basis for differential targeting properties of small RNAs in plants and animals
Yao Xiao,Ian J. MacRae +1 more
TL;DR: Tiny structural differences can tune the targeting properties of AGO proteins for distinct biological roles and HsAGO2 can be engineered for potential applications in siRNA therapeutics.
Dissertation
Chitosan-based nanocarriers for gene- and siRNA-delivery
TL;DR: The results show that the most efficient gene silencing was achieved using fully de-N-acetylated chitosans with intermediate chain lengths (DPn 100-300), which mediated efficient siRNA delivery at low siRNA concentrations and, in several cell lines, potent long-term silencing of both exogenous and endogenous target genes, with minimal cytotoxicity.
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.