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A dynamic integrated research program focused on basic research, diagnostics (human and veterinary), therapeutics and public health and safety has resulted in an extensive proprietary technology portfolio including amongst others:

Conditions for preparing a monomeric, soluble and stable recombinant human prion protein, rich in β-sheet structure and designated β−PrP have been established. β−PrP has many properties in common with the disease-associated form of the prion protein PrP^Sc. It has potential applications in research, diagnostics, prophylaxis and therapeutics.

A core region of PrP^c has been identified that resists denaturation. The ability to make peptides of this region and antibodies that recognise them has potential uses in the diagnosis, prevention and treatment of prion disease.

A diagnostic test that allows rapid molecular diagnosis and differentiation of sporadic and iatrogenic CJD from variant CJD in humans has been developed. This allows for relevant classification of human prion disease and its aetiology. The test is important for both diagnostic and public health planning purposes.

Genetic biomarker tests are being developed to indicate potential susceptibility to vCJD in humans. Such approaches will be used for diagnosis and for population risk assessment studies.

Prions are extremely resistant to heat and chemicals rendering most existing sterilisation technologies ineffective in their deactivation. Conditions normally used for inactivating prions - typically powerful oxidising agents or strong alkalis - are highly corrosive to the instruments and washing equipment used in hospital sterilisation units. Prions have been shown to bind avidly to surgical stainless steel and act as a source of infectivity. The prolonged incubation periods for human prion disease mean that individuals may be symptomatic but infectious for more than a decade leading to increased risks of iatrogenic transmission - a formidable public health challenge. A practical enzyme-based decontamination technology has been developed and extensively tested both in-vitro and in-vivo. Results show that the introduction of this technology as a pre-treatment in the sterilisation process would reduce the risk of iatrogenic transmission by at least five orders of magnitude over and above the reduction in infectivity afforded by autoclaving.

Currently the gold standard for measuring prion infectivity is animal bioassay based on intracerebral inoculation of mice that is slow (~140 days) and costly. A quantitative in-vitro assay for prion infectivity, the scrapie cell (SC) assay has been developed. This assay is about as sensitive as the mouse bioassay, 10 times faster (14 days), orders of magnitude less expensive and suitable for robotization and high throughput. To date the SC assay can be used to determine infectivity titres of mouse brain homogenates (RML). The SC assay will be particularly useful for prion clearance or reduction studies on manufacturing processes using bovine derived tissues or human blood products.

The effective suppression of peripheral prion replication using antibody therapy has been achieved. Two novel D-Gen monoclonal antibodies ICSM18 and ICSM35 have been demonstrated to prevent the development of prion disease in an in vivo mouse model system. This demonstrates the potential of using antibodies as immunotherapeutics to prevent and treat prion disease.

A long standing limitation of anti-PrP monoclonal antibodies has been their inability to recognise the disease associated isoform of PrP, PrP^Sc. Although several commercial antibodies are capable of reacting with denatured PrP^c and PrP^Sc on western blots, antibodies capable of detecting native PrP^Sc for use in FACS analysis, immunoprecipitation or in vivo studies have not been available. Utilising a novel recombinant immunogen several unique antibody specificities were identified and are now available. These monoclonal antibodies can react with both PrP^c and /or PrP^Sc in the native or denatured forms. The availability of these antibodies will be useful for basic research, diagnostics and possibly therapy.

D-Gen seeks to exploit its inventions and technologies by bringing them to market through complementary collaborations and partnerships in a global context.

The NEW rapid and sensitive Prion-Screen BSE test from Roche Diagnostics uses the D-Gen ICSM18 and ICSM35 monoclonal antibodies. Prion-Screen has been developed for routine BSE diagnostics and is expected to be available soon. The microplate format test has been designed for both manual and automated use to satisfy different laboratory throughput and workflow requirements.