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Issue 2 2009
Issue 2 2009 / 20 March 2009 /
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 trials, which tragically led to several deaths. Despite early failures in the development of gene therapies, work in this field has continued, and the promise of life saving treatments remains.
Early gene therapy strategies consisted primarily of the introduction of a functional gene to compensate for a mutated or otherwise nonfunctional endogenous allele. While this approach is appropriate for many serious conditions, such as hemophilia and X-linked severe combined immunodeficiency (X-SCID), genetic diseases caused by the inappropriate upregulation of gene expression cannot be addressed by this method. An alternative approach designed to treat diseases caused by upregulated gene expression is antisense therapy, a process whereby an RNA molecule is introduced which hybridises to the mRNA of the upregulated gene in question, blocking its translation1. (more…)
Tagged with: Kevin V. Morris, microRNA, Peter Hawkins, RNA, RNAi, The Scripps Research Institute
Issue 2 2009 / 20 March 2009 /
The fluorescence-based quantitative real-time polymerase chain reaction (qPCR)1-3, is the most widely used method to detect and measure minute amounts of DNA in a wide range of samples extracted from numerous sources. Since all currently available thermostable polymerases are DNA-dependent, RNA must be converted (“reverse transcribed”) into DNA prior to its amplification reaction. Both qPCR and reverse transcription (RT)-qPCR have revolutionised life sciences, agriculture, medical research and diagnostic and forensic applications4,5.
However, the adoption of protocols combining RT and qPCR necessitates acceptance of assumptions carried through from legacy RT-PCR; primarily that the process of RT is reproducibly quantitative, linear and maintains proportionality between genes when the cDNA for each is produced. It has become apparent that each of these assumptions requires further qualification before total adoption of any protocol is appropriate. In addition, the degree to which different protocols, RT enzymes and priming strategies influence quantitative assessments also requires clarification. (more…)
Tagged with: qPCR, Sigma-Aldrich, Stephen Bustin, Tania Nolan
Issue 2 2009 / 20 March 2009 /
Generating knowledge and insight from complex genomic data sets is always a challenging endeavor. As data collection becomes more routine and less expensive, and the existing body of data expands, getting the most out of genomics experiments requires ever more expertise and insight. Here, we discuss our method of integrating gene expression profiling data for a candidate oncology drug with pre-existing data and the knowledge and expertise of a wide variety of biologists and statisticians.
A current genomics lab often has access to a wide variety of genomics techniques, including expression profiling via qRT-PCR, mRNA microarrays, and miRNA microarrays; gene knockdown via siRNA and miRNA mimics; a number of pathway tools, and statistical/visualisation programs. In addition, public sources of data and years of accumulation of in-house data allow additional insight. Incorporating these types of data is now standard in drug discovery programs for target identification, mechanism of action studies, toxicity analysis and biomarker discovery. (more…)
Tagged with: Biomarkers, Charu Kanwal, Holly Hilton, qPCR, Roche, Windy Berkofsky-Fessler
Issue 2 2009 / 20 March 2009 /
Dr Paul Andrews (Senior Scientist, ITI Stem Cell Technology Programme, University of Dundee), Professor Peter Andrews (co-Director of the Centre for Stem Cell Biology, University of Sheffield), Fergus McKenzie PhD. (Programme Manager, ITI-Life Sciences), Dr Stephen Minger (Senior Lecturer in Stem Cell Biology, Kings College London) and Will Rust (Section Manager, Cell Systems R&D, Lonza Bioscience) take part in a roundtable to discuss stem cell research. (more…)
Tagged with: Fergus R. McKenzie, Kings College London, Lonza, Paul Andrews, Peter Andrews, Stem Cells, Stephen Minger, University of Dundee, University of Sheffield, Will Rust
Issue 2 2009 / 20 March 2009 /
Technological advances in robotised microscopy, liquid handling and image processing have enabled the emergence of high content screening where large numbers of specimens are automatically analysed. Here we overview the process discussing potential difficulties and solutions.
High content screening (HCS) enables the discovery of novel regulators of biological and physiological processes in an unbiased manner using light microscopy imaging. (more…)
Tagged with: Cancer Research UK, Daniel Zicha, HCA (High Content Analysis), Imperial College, Olivier E. Pardo
Issue 2 2009 / 20 March 2009 /
There has been a continuous move by the large commercially orientated players involved in Drug Discovery to initiate novel methods to increase income streams and productivity. An example of the former has been the acquisition of companies and their drug pipelines and in the case of the latter, rationalisation of internal Research & Development activities. This is well illustrated by GlaxoSmithKline Pharmaceuticals which have formed small focused research units called the Centres for Excellence in Drug Discovery (CEDD) and the Discovery Performance Units (DPU) each of which having increased accountability1.
Many of the small molecule entities discovered in the pre-clinical phases of Drug Discovery have been identified from compound screening activities (CSA) e.g. Low Throughput Screening (LTS) usually employing focussed sets of compounds (numbering in the low tens of thousands) and High Throughput Screening (HTS) utilising significantly larger libraries (in the hundreds of thousands and in some cases in the region of one million compounds)2-5. These CSA require two inputs, namely an assay and high quality compound library. Up until relatively recently, most of the microtitre plate based CSA were carried out in an in vitro biochemical format that used targets in a purified form (tagged truncate or full length) prepared from recombinant expression systems. Crude preparations will also suffice, however, appropriate control experiments are required to ensure the measured modulation of target activity in the presence of compound is not due to a contaminant within the preparation. Of course, assays for transporters, ion-channels, and receptors would be in a cell membrane or cellular system. These in vitro biochemical assays tend to be a context far removed from actual physiological conditions6. More recently, human primary and stem cell based assays are becoming more common in CSA7-9. In order to enhance the outputs from these assays, High Content Screening (HCS) can also be used to yield phenotypic read-outs (e.g. changes in morphology, sub-cellular localisation and redistribution of proteins)10. The second component required for CSA, the high quality compound library, would be expected to contain known scaffolds (for LTS) or diverse chemical space (for HTS) that contain appropriate starting points for Drug Discovery. (more…)
Tagged with: European ScreeningPort, Lab Automation, Sheraz Gul
Issue 2 2009 / 20 March 2009 /
The 15th annual SBS conference and exhibition will be held in Lille, the capital of the Nord-Pas-de Calais region in Northern France. 2009 is a momentous year for SBS as it is the 15th anniversary of the formation of the Society and to celebrate the occasion this year’s theme will be ‘Bioassay & Technology Innovation: 15 Years of shaping Drug Discovery’. (more…)
Tagged with: SBS, Show Preview
Issue 2 2009 / 20 March 2009 /
Peptides and proteins are powerful active therapeutic ingredients used in a wide variety of serious conditions and illnesses such as diabetes, arthritis or cancer. The application of these so-called biopharmaceuticals has been rapidly increasing since the middle of the 1990s, facilitated by improvements in modern recombinant DNA technology and biotechnological manufacturing. The worldwide sales of the biotech drug market grew from 43 billion US$ in 2003 to over 75 billion US$ in 2007 according to a recent IMS Health market analysis. The major challenge in the development of stable protein formulations and dosage forms is to ensure their process and shelf life stability.
The fact that these biological macromolecules have several levels of structure, referred to as primary, secondary, tertiary and quaternary structure (see Box 1), constitute the basis for multiple interaction pathways that can lead to protein instability1. Damage to at least one type of these substructures is referred to as denaturation and can greatly reduce protein functionality2. As water supports many degradation pathways (e.g. hydrolysis, oxidation or deamidation), long term storage stability of aqueous protein solutions is often limited3. The primary approach to elongate their shelf life is to reduce water availability and activity. This can be achieved to some extend by freezing, but the most desirable approach is to completely remove water and transfer the aqueous protein formulation into a dry powder form. (more…)
Tagged with: Freeze Drying, Heiko Schiffter, Sebastian Vonhoff, University of Erlangen-Nuremberg, University of Oxford
Issue 2 2009 / 20 March 2009 /
On the cold and snowy weekend of the 7th and 8th of February a group of academics, professionals and vendors met in Dublin for the first Cellular Imaging and Analysis event co-hosted by Trinity College Dublin and the European Pharmaceutical Review. Battling through the adverse weather conditions, delegates and speakers came from faraway places such as North Carolina and Goettingen and nearer corners of the British Isles such as Edinburgh and London. (more…)
Tagged with: CIA (Cellular Imaging and Analysis), Show Preview
Issue 2 2009 / 20 March 2009 /
Quality risk management (QRM) is an important part of science-based decision making which is essential for the quality management of pharmaceutical manufacturing1. The ICH Q9 guideline, Quality Risk Management2 defines QRM as a systematic process for the assessment, control, communication and review of risk to the quality of drug product across the product lifecycle. Similarly, the FDA Final Report for Pharmaceutical cGMPs for the 21st Century – A Risk-Based Approach3, states that using a scientific framework to find ways of mitigating risk while facilitating continuous improvement and innovation in pharmaceutical manufacturing is a key public health objective, and that a new risk-based pharmaceutical quality assessment system will encourage the implementation of new technologies, such as process analytical technology (PAT), to facilitate continuous manufacturing improvements via implementation of an effective quality system.
The FDA’s PAT Guidance, which was finalised in 20044, describes a regulatory framework that will encourage the voluntary development and implementation of innovative approaches in pharmaceutical development, manufacturing, and quality assurance. Many new technologies are currently available that provide information on physical, chemical, and microbiological characteristics of materials to improve process understanding and to measure, control, and/or predict quality and performance. The guidance facilitates the introduction of such new technologies to improve efficiency and effectiveness of manufacturing process design and control, and quality assurance. A desired goal of the PAT framework is; therefore, to design and develop well-understood processes that will consistently ensure a predefined quality at the end of the manufacturing process, which is the foundation for the concept, that quality cannot be tested into products; it should be built-in or should be by design.
(more…)
Tagged with: Michael J. Miller, Microbiology, Microbiology Consultants LLC
Issue 2 2009 / 20 March 2009 /
Date: 11-15 May 2009
Venue: Exhibition grounds of Messe Frankfurt GmbH
Website: www.achema.de
At ACHEMA ideas are born, decisions made and the course is set.
Back for the 29th time, Achema 2009 will be the worldwide leading event for chemical engineering and the process industries. With 4,000 exhibitors from every continent, 180,000 participants from 100 countries and 30,000 executives, it is set to be a huge affair. (more…)
Tagged with: ACHEMA, Show Preview
Issue 2 2009 / 20 March 2009 /
DATE: 31 May – 4 June 2009
VENUE: Pennsylvania Convention Centre, Philadelphia
WEBSITE: www.asms.org
The program will begin on Sunday 31 May with tutorial lectures at 5pm and the opening session and plenary lecture at 6.45pm. (more…)
Tagged with: ASMS, Show Preview
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