Journal ArticleDOI
Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application.
Reads0
Chats0
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
More filters
Journal ArticleDOI
Small interfering RNA targeted to IGF-IR delays tumor growth and induces proinflammatory cytokines in a mouse breast cancer model.
Tiphanie Durfort,Tiphanie Durfort,Mercedes Tkach,Mariya I. Meschaninova,Martín A. Rivas,Patricia V. Elizalde,Alya G. Venyaminova,Roxana Schillaci,Jean Christophe Francois,Jean Christophe Francois +9 more
TL;DR: The findings show that silencing IGF-IR using synthetic siRNA bearing 2′-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF- IR, and suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines.
Journal ArticleDOI
Exploring RNAi as a therapeutic strategy for controlling disease in aquaculture
TL;DR: The present review discusses the current knowledge of RNAi as an experimental tool, as well as the concerns and challenges ahead for the application of such technology to combat infectious disease of farmed aquatic animals.
Journal ArticleDOI
Gene suppression approaches to neurodegeneration
Rhia Ghosh,Sarah J. Tabrizi +1 more
TL;DR: The main developments in gene suppression strategies are summarized, using examples from Huntington’s disease and other inherited causes of neurodegeneration, and how these might illuminate a path to tackle other proteinopathy-associated dementias in the future are explored.
Journal ArticleDOI
Delivery of intracellular-acting biologics in pro-apoptotic therapies.
TL;DR: The molecular mediators of cellular apoptosis, the respective mechanisms by which these mediators are dysregulated in cellular oncogenesis, the history and development of both nucleic-acid and amino-acid based drugs, and techniques to achieve intracellular delivery of these biologics are discussed.
Journal ArticleDOI
High-Throughput Silencing Using the CRISPR-Cas9 System: A Review of the Benefits and Challenges.
TL;DR: It is envisaged that complementarities between CRISPR, siRNA, and shRNA will ensure that all three technologies remain critical to the success of future functional genomics projects.
References
More filters
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.