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Putting the ‘fun’ into functional genomics: a review of RNAi genomewide cellular screens

18 December 2012 | By Dr. Stephen Brown, Sheffield RNAi Screening Facility, Biomedical Sciences, University of Sheffield

As RNA interference (RNAi) enters its teenage years from the first critical observations, it has now reached a multi-billion pound industry. There are few research areas that have expanded as quickly and spectacularly as the field of RNAi. The potential of RNAi initially sparked a functional genomics gold rush. Different…

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Ten years of siRNA – a clinical overview

10 July 2012 | By Katharina Bruno, Principal Scientist, Technical Research & Development (TRD), Novartis Pharma AG

In 2001, small interfering RNA (siRNA) was discovered as the mediator of RNA interference (RNAi), a transient and specific repression mechanism of protein expression1. After the pharmaceutical industry became aware of the intrinsic versatility and potential of this molecule, a race to develop the first siRNA based drug began. However,…

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microRNA manipulation as a host-targeted antiviral therapeutic strategy

13 December 2011 | By Nouf N. Laqtom, University of Edinburgh & King Abdulaziz University and Amy H. Buck, University of Edinburgh

microRNAs (miRNA) are a class of non-coding RNA that regulate the precise amounts of proteins expressed in a cell at a given time. These molecules were discovered in worms in 1993 and only known to exist in humans in the last decade. Despite the youth of the miRNA field, miRNA…

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Unconventional RNA interference – recent approaches to robust RNAi

19 October 2011 | By Marie Lundbæk, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology and Pål Sætrom, Department of Cancer Research and Molecular Medicine & Department of Computer and Information Science, Norwegian University of Science and Technology

RNA interference (RNAi) is now a standard tool in molecular biology. Short interfering RNAs (siRNAs) for knocking down your favourite human gene are only a couple of mouse-clicks away at your favourite reagent supplier’s website. Moreover, in contrast to initial attempts at siRNA design, these siRNAs usually give potent target…

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RNAi screens for the identification and validation of novel targets: Current status and challenges

16 December 2010 | By Attila A. Seyhan, Translational Immunology, Inflammation and Immunology, Pfizer Pharmaceuticals

Recent advances in RNA interference (RNAi) technology and availability of RNAi libraries in various formats and genome coverage have impacted the direction and speed of drug target discovery and validation efforts. After the introduction of RNAi inducing reaagent libraries in various formats, systematic functional genome screens have been performed to…

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Functional genomics as a tool for guiding personalised cancer treatment

29 October 2010 | By Roderick Beijersbergen, Group Leader Molecular Carcinogenesis, the Netherlands Cancer Institute

Improved understanding of the molecular alterations in cancer cells has fuelled the development of more specific and directed cancer therapies. However, it has become clear that response rates can be low due to confounding genetic alterations that render these highly specific therapies ineffective. As a result, the costs of cancer…

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The evolution of RNAi technologies in the drug discovery business

29 October 2010 | By Jason Borawski and L. Alex Gaither, Novartis Institutes for Biomedical Research

In the past decade, the pharmaceutical industry has exploited the naturally occurring cellular RNAi pathway to enhance drug discovery research. The RNAi pathway, triggered by dsRNA, selectively, although not always specifically, degrades mRNA leading to substantial decreases in post-transcriptional gene expression1. Researchers have capitalised on this intrinsic pathway by synthesising…

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RNAi-based therapies for the treatment of HIV

24 June 2010 | By Marc S. Weinberg and Fiona van den Berg, Antiviral Gene Therapy Research Unit, Department of Molecular Medicine and Haematology, University of Witwatersrand

Since the discovery of RNA interference (RNAi) in 1998 and the demonstration of RNAi in mammalian cells in 2001, research into the mechanisms and applications of this pathway has moved swiftly. RNAi is capable of mediating potent and specific silencing of genes and has therefore shown promise in the development…

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RNAi screening in the era of high-throughput genetics

12 December 2009 | By

The use of RNAi screening to identify potential drug targets has enjoyed great success in recent years as a robust method for linking genes to a disease process through a functional assessment of a gene in an experimental model1. True, RNAi screening is complicated by problems such as off-target effects…

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RNAi applications in biology and medicine

30 July 2009 | By

The field of oligonucleotide-based therapy experienced a revival with the discovery of RNA interference (RNAi) in 19981. RNAi is a conserved endogenous mechanism, which is triggered by double-stranded (ds) RNAs leading to target-specific inhibition of gene expression by promoting mRNA degradation or translational repression. There are two RNAi pathways that…

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Small non-coding RNAs as therapeutics

20 March 2009 | By

For years biologists have worked to develop alternatives to traditional therapeutics. These efforts, in areas such as stem cell based and gene therapies, have received much fanfare in popular media outlets, raising expectations among the general public. This excitement may have contributed to the hasty progression of early gene therapy…

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miRNA and viral infections in vertebrates

7 February 2009 | By

For plants and invertebrates, RNA interference is firmly established as an important antiviral mechanism. Even before Fire, Mello, and co-workers described RNA interference (RNAi) in worms in 19981 it was becoming clear that plants have an RNA-dependent pathway that protects against viral infections2. The pathway, then termed post-transcriptional gene silencing…

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RNAi therapeutics: addressing targets?

2 August 2008 | By

Gene silencing by RNA interference (RNAi) uses double-stranded RNA to shut down gene expression in cells. This provides the possibility that this new methodology could be used in the treatment of disease symptoms and disease processes. A particular attraction of RNAi (as well as other gene knockdown methods of treatment,…