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

The production of recombinant proteins for medical research and healthcare is a rapidly
expanding area of biotechnology. However, many of these proteins must be manufactured in
expensive mammalian systems to ensure correct protein folding, where the yield is typically
low in comparison to bacterial systems (usually 100-1000-fold lower). In part this is due to the
inferior strength of mammalian promoters (that control protein production) in comparison to
bacterial counterparts.
The strength of bacterial promoters is easy to predict, and the amount of protein produced is
often proportional to how similar the promoter used is to the ‘optimal’ consensus promoter. In
mammalian promoters, these same predictions cannot be made because the structures are
much more complex, making it difficult to know which sections of the promoter might
enhance protein production. As a result, most mammalian expression systems are based on
naturally-occurring ‘wild-type’ promoters, which have actually evolved for physiological
functions, not commercial protein manufacture. Our preliminary data show that significantly
stronger promoters can be developed using our technology, with significant implications for
protein manufacture.
At Oxford Genetics Ltd we have developed a ‘bioselection’ cloning system called
‘Prometheus’ to screen large numbers (>4000) of recombinant mammalian promoters. The
technique allows a wide array of strong ‘wild-type’ mammalian promoters to be ‘shuffled’ and
screened to identify new composite promoters that produce more protein than the current gold
standards, CMV and CAG. Preliminary results are exciting, and in this project we aim to
develop ‘superstrength’ promoters that will dramatically improve the productivity of
transgenes, including proteins and antibodies for manufacture.