Engineering highly efficient promoters for eukaryotic protein production, tissue specific expression, and biomedical pathway analysis by Oxford Genetics Ltd

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The production of recombinant proteins for medical research and healthcare is a rapidlyexpanding area of biotechnology. However, many of these proteins must be manufactured inexpensive mammalian systems to ensure correct protein folding, where the yield is typicallylow in comparison to bacterial systems (usually 100-1000-fold lower). In part this is due to theinferior strength of mammalian promoters (that control protein production) in comparison tobacterial counterparts.The strength of bacterial promoters is easy to predict, and the amount of protein produced isoften proportional to how similar the promoter used is to the ‘optimal’ consensus promoter. Inmammalian promoters, these same predictions cannot be made because the structures aremuch more complex, making it difficult to know which sections of the promoter mightenhance protein production. As a result, most mammalian expression systems are based onnaturally-occurring ‘wild-type’ promoters, which have actually evolved for physiologicalfunctions, not commercial protein manufacture. Our preliminary data show that significantlystronger promoters can be developed using our technology, with significant implications forprotein manufacture.At Oxford Genetics Ltd we have developed a ‘bioselection’ cloning system called‘Prometheus’ to screen large numbers (>4000) of recombinant mammalian promoters. Thetechnique allows a wide array of strong ‘wild-type’ mammalian promoters to be ‘shuffled’ andscreened to identify new composite promoters that produce more protein than the current goldstandards, CMV and CAG. Preliminary results are exciting, and in this project we aim todevelop ‘superstrength’ promoters that will dramatically improve the productivity oftransgenes, including proteins and antibodies for manufacture.