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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Synthesis and characterization of AICAR and DOX conjugated multifunctional nanoparticles as a platform for synergistic inhibition of cancer cell growth
TL;DR: Results indicate that the multifunctional nanoparticle system possesses high inhibitory drug association and sustained cytotoxic effect with good biocompatibility, which might be promising as an antitumor treatment for cancer.
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Hierarchical Assembly of siRNA with Tetraamino Fullerene in Physiological Conditions for Efficient Internalization into Cells and Knockdown.
TL;DR: It is found in this in vitro study that hierarchical reversible assembly of micrometer-sized TPFE-siRNA-serum protein ternary complexes is the key element for effective loading and release, and stabilization of otherwise highly unstable siRNA under the physiological conditions.
Journal ArticleDOI
Minireview: Switching on progesterone receptor expression with duplex RNA.
TL;DR: Evidence now supports the existence of regulatory pathways that use small duplex RNAs to control transcription, and focuses on the robust and potent agRNA-mediated regulation of progesterone receptor.
Journal ArticleDOI
Progranulin contributes to endogenous mechanisms of pain defense after nerve injury in mice
TL;DR: It is found that progranulin is up‐regulated after injury of the sciatic nerve in the mouse ipsilateral dorsal root ganglia and spinal cord, most prominently in the microglia surrounding injured motor neurons.
Journal ArticleDOI
C7: a CpG oligodeoxynucleotide that induces protective immune response against megalocytivirus in Japanese flounder (Paralichthys olivaceus) via Toll-like receptor 9-mediated signaling pathway.
Zhi-xia Zhou,Jian Zhang,Li Sun +2 more
TL;DR: Results indicate that ODN C7 activates TLR9-mediated immune response and possesses antiviral and adjuvant potentials that may be exploited for the control of megalocytivirus infection in farmed flounder.
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.