University of Oxford - Articles and news items

The determination of structural changes of biopharmaceuticals during Freeze-Drying using Fourier Transform Infrared Spectroscopyb

Issue 2 2009, Past issues / 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…)

RNAi therapeutics for neurodegenerative disease: challenges and prospects

Issue 2 2008, Past issues / 19 March 2008 /

The early 21st century has seen a revolution in RNA biology, bringing with it the prospect of a new class of medicines based on RNA. What are the prospects for developing these RNA-based medicines for the growing medical problem of neurodegenerative disease and what are the challenges to making these new medicines work successfully within the complex environment of the nervous system? Recent progress on RNA silencing of neurodegenerative disease targets and RNAi delivery to the nervous system is encouraging and suggests that clinical evaluation of these therapeutic agents is realistic within the next few years.

A spectacular revolution in RNA biology over the last decade has created new tools and opportunities for advancing basic biomedical science as well as the tantalising prospect of RNA-based medicines to treat human disease. The discovery of RNA interference (RNAi) in 1998 by Fire and Mello1 led rapidly to elucidating the biochemical mechanism underlying the phenomenon of RNA-based gene silencing. (more…)

Spray-freeze-drying in the manufacture of pharmaceuticals

Issue 3 2007 / 23 May 2007 / Heiko A. Schiffter, Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford

Over the last decade, the development of new drug delivery methods and devices for dry powder inhalation1, needle-free intradermal powder injection2 or sustained parenteral drug delivery3 has led to an increasing demand for powder formulations incorporating an active pharmaceutical ingredient (API)4,5. (more…)

Structural genomics, the practical way

Issue 4 2006, Past issues / 20 July 2006 / Frank von Delft, Principle Investigator, Protein Crystallography Group, Structural Genomics Consortium, University of Oxford

The Structural Genomics Consortium (SGC) is an internationally funded collaboration with sites in three countries and a three-year goal of solving the 3-dimensional structures of more than 380 human proteins with particular medical relevance, and placing them in the public domain without restrictions. The structures should prove an invaluable resource for research into the proteins’ functions and their use as targets for therapeutic intervention; in this the SGC is a successor to the Human Genome Project (HGP). The SGC has benefited from adopting existing, commercialised robotics, and is subsequently working with vendors to adjust performance with its needs.

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Options for quantitative analysis by real-time PCR

Issue 4 2005, Past issues / 11 November 2005 / Gareth Elvidge, PhD, Genomics Group, Wellcome Trust Centre for Human Genetics, University of Oxford

The expansion of microarray-based gene expression studies has led to an increase in demand for gene-specific PCR-based methods for independent validation of results. Although a number of technologies are available to meet this requirement the most popular is currently real-time PCR.

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