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
Development of Guanidinium-Rich Protein Mimics for Efficient siRNA Delivery into Human T Cells.
TL;DR: By evaluating the PTDM design parameters for siRNA delivery, more efficient PTDMs were discovered that improved delivery and gene (NOTCH) knockdown in T cells, which should aid in the exploration of T cell molecular pathways leading eventually to new therapeutics.
Journal ArticleDOI
Cell Reprogramming With CRISPR/Cas9 Based Transcriptional Regulation Systems.
TL;DR: The aim of this article is to summarize currently existing CRISPR/Cas9 applications for cell reprogramming, mainly, to compare them with other non-CRISPR approaches and to highlight future perspectives and opportunities.
Journal ArticleDOI
Functionally Enhanced siRNA Targeting TNFα Attenuates DSS-induced Colitis and TLR-mediated Immunostimulation in Mice
Sandra M. Ocampo,Carolina Romero,Anna Aviñó,Joan F. Burgueño,Miguel Angel Gassull,Jordi Bermúdez,Ramon Eritja,Ramon Eritja,Ester Fernández,Jose C. Perales +9 more
TL;DR: It is demonstrated that propanediol and 2'-O-methyl modifications have profound functional consequences for siRNA efficacy in vivo and has potential implications for therapeutic intervention in IBD and other diseases.
Journal ArticleDOI
Enhancer-associated RNAs as therapeutic targets.
TL;DR: As key factors in the control of transcription, eRNAs appear to possess a great potential for the establishment of new therapy options, however, thorough testing as well as providing the genetic toolbox to target e RNAs will be needed to fully assess the practical and clinical possibilities.
Book ChapterDOI
Alternative Splicing in Genetic Diseases: Improved Diagnosis and Novel Treatment Options.
TL;DR: The current state of molecular mechanisms of splicing regulation and how deregulation can lead to human disease, diagnostics to detect splicing variants, and novel treatment options based on splicing correction are reviewed.
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.