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Country of origin: United Kingdom

Summary

A UK biotech company offers a rapid, inexpensive assay system allowing the identification of genes and proteins that inhibit apoptosis from any human tissue or organ. Validation studies carried out on a human hippocampal cDNA library in yeast discovered 16 apoptosis-inhibitory proteins, some already known to be linked with apoptosis, others that have been linked to neurodegenerative diseases and others that have never previously been linked to apoptosis. Licensing agreements are sought.

Full description

The technology is a rapid and inexpensive assay based upon a yeast system. Essentially, a human c-DNA library derived from a human tissue of choice is cloned in a yeast expression vector to generate representative libraries. The resulting library of plasmids is transformed into a specific strain of yeast cells that contain a copy of a Bax expression cassette. The Bax gene codes for a pro-apoptotic protein which initiates apoptosis. The Bax-containing yeast strain cannot grow (i.e. cells die showing apoptotic features) if Bax is expressed (no background growth which could have been caused by revertants even after screening >1010 cells) but the cells survive if they simultaneously express an anti-apoptotic protein. As the anti-apoptotic protein is already encoded by a cDNA on a plasmid, the genetic sequence can be readily identified.
After sequencing the c-DNA insert on the plasmid, the sequence is searched in the human genome data base to see if the anti-apoptotic gene/protein has already been described or if it is novel. That the identified anti-apoptotic gene/protein can also rescue mammalian apoptosis can then be confirmed by transfecting the gene into appropriate human cell lines and measuring apoptosis using conventional assays such as detection of DNA Fragmentation by the TUNEL assay, determination of cytochrome c release from mitochondria by in situ immunofluorescence, measurement of mitochondrial membrane potential or by simply determining the absence of Bax-mediated cell death.
Patent applications to protect the technology have been filed and are undergoing examination.
The company is looking to license the technology to a company specialising in CNS diseases.

Innovative Aspects

The technology allows the discovery of novel disease-related proteins. The assay is rapid and relatively inexpensive to carry out. New proteins and genes identified through the assay will be linked to a certain function: they will share the ability to inhibit apoptosis in specific cellular contexts. However, the discovered proteins and genes may have no structural and sequence similarities. In contrast, classical functional genomics/proteomics programmes attempt to identify new members of known protein families in the Human Genome database via motifs, domains and folds that structurally define already known classes of proteins.

The technology is proven and has already produced useful results. A company engaged in CNS research/development could rapidly start identifying genes and proteins associated with disease states.

Partner expertise sought:

- Type of partner sought: Industry.

- Specific area of activity of the partner: CNS drug discovery.

- Task to be performed by the partner sought: Research, development and commercialisation.

Listed under: Life Sciences \ Biosciences and Health \ Engineering \ Drug Discovery and Drug Development \ Diagnostics \ Medical Devices

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Key dates Profile created on: 27 July 2010 Closing date: 20 July 2011

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