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siRNA Therapeutics - Articles and news items
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 query the functions of individual genes, pathways or an entire genome in many disease areas, including cancer, viral pathogenesis and others. As a consequence of these screens, novel mediators of cellular response to disease pathogenesis or treatment approaches have been identified leading to the discovery of novel drug targets, development of combinatorial treatment approaches and patient selection biomarkers.
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 RNAi reagents to modify the expression of any desired gene. RNAi libraries consisting of synthetic siRNAs or plasmid based shRNAs are amendable to largescale genome-wide screening campaigns to search for new therapeutic targets. Such loss of function screens can reveal novel targets and synthetic lethal interactions for cancer therapy2,3. These screens have also been used to identify novel host factors for diseases such as Hepatitis C4-7 and HIV8-14. Selective gene silencing can deconvolute molecular pathways implicated in disease onset and progression15.
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 of alternative anti-viral therapies with the potential to avoid disadvantages associated with conventional drug regimens. A number of synthetic and expressed constructs have been investigated against HIV with varying success. Despite rapid progress, important hurdles need to be surmounted before a safe, effective and widely applicable therapy can be implemented clinically. Here, we review different RNAi-based strategies against HIV and highlight future developments necessary for the realisation of an effective anti-HIV therapy…
Non-coding RNAs (ncRNAs) consist of a growing heterogeneous class of transcripts defined as RNA molecules that lack any extensive “Open Reading Frame” (ORF) and function as structural, catalytic or regulatory entities rather than serving as templates for protein synthesis. While non-coding sequences make up only a small fraction of the DNA of prokaryotes, among eukaryotes, […]
Issue 3 2007 / 23 May 2007 / John J. Rossi, Division of Molecular Biology, Beckman Research Institute of the City of Hope, Graduate School of Biological Sciences, Duarte, United States
RNA interference (RNAi) is a regulatory mechanism of most eukaryotic cells that uses small double stranded RNA (dsRNA) molecules as triggers to direct homology-dependent control of gene activity (Almeida and Allshire 2005).
Small interfering RNAs are irreplaceable tools for the functional analysis of pathological gene products. Therapeutic siRNA development leads to new treatment strategies for gene products, where conventional small molecule approaches have failed.
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