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siRNA - Articles and news items
Supplier news / 24 February 2016 / Biopharma Group
Liposomes are valued delivery vehicles for potent and efficacious active pharmaceuticals…
Issue 3 2012, Screening / 10 July 2012 / Anthony Mitchell Davies & Anne Marie Byrne, Department of Clinical Medicine Trinity College Dublin; Holger Erfle, BIOQUANT-Zentrum Ruprecht-Karls-Universität Heidelberg; Graham Donnelly, Rita Murray & Peadar MacGabhann, Biocroi Ltd
One of the major limitations of performing large-scale High Content Analysis (HCA) screens is reagent cost, indeed this fact has been a key driver in the development of assay size reduction strategies here at The Irish National Centre for High Content Screening and Analysis at Trinity College’s Department of Medicine.
As well as the obvious financial advantages of reducing assay volumes, we have also identified other key benefits to this approach, namely: Higher throughput; Improved signal to noise; Suited for the use of valuable cells, e.g. primary cells; Reduced storage and research space; Improved mixing of reagents.
The practicalities of performing cell based assays at the nano-litre scale: Despite the clear benefits to adopting miniaturisation, there are several significant barriers that must be overcome before these methods can be utilised. These are sample delivery / handling and environmental stability.
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, the initial hype was followed by the realisation that due to the specific properties of this very fragile molecule, stability and delivery issues might limit its application to certain niche indications.
siRNAs have been rushed into the clinics before fully understanding their biological effects. As a result, some of the big pharmaceutical companies such as Roche or Pfizer, who were initially committed to siRNA drug development, have meanwhile scaled back their efforts or entirely stopped their siRNA programs.
An important property of siRNA to be controlled during the drug discovery process is its potential off-target effect, which limits its specificity. The key to developing a successful drug based on a well characterised siRNA molecule is its formulation, since the molecule is relatively big, heavily charged and susceptible to degradation in the body fluids, therefore, the delivery vehicle has to provide protection as well as enable cell penetration and release. An overview of the delivery-enabling excipients which have progressed into clinics can be found elsewhere2. Although so far no siRNA based therapeutic product has been commercialised, several clinical trials have been conducted or are currently on-going.
Genomics, Issue 5 2011 / 19 October 2011 / 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 gene knockdown. Nevertheless, siRNAs are not always a cure-all; therapeutic settings often require combinatorial treatments and may necessitate effects that are incompatible with standard siRNAs, such as targeted gene up-regulation. Here, we review the features of standard siRNAs before describing three unconventional but therapeutically relevant approaches to RNAi: multi-targeting siRNAs, immunostimulatory siRNAs, and transcription-modulating siRNAs.
Fire and Mello coined the term RNA interference when they discovered that long doublestranded RNAs cause sequence specific gene inhibition in worms1,2. The enzyme Dicer processes such long double-stranded RNAs into short double-stranded ~22 nt duplexes with 2 nt 3’ overhangs – the siRNAs. Argonaute 2 (Ago2) then incorporates one of the siRNA strands and uses the strand as a guide to bind and cleave single-stranded RNAs such as messenger RNAs (mRNAs).
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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