Oxford Identifies New Tool for Protein Expression

8th May 2009

Oxford University Innovation, the technology transfer arm of the University of Oxford has released details of a new method for increasing protein production, with the potential to improve the efficiency of drug manufacturing by multi-fold increases in yields of therapeutic proteins. The method, developed at Oxford’s Sir William Dunn School of Pathology, was profiled in the journal Cell.

The technology has been tested in standard mammalian cell systems, and early data shows yields of the hormone erythropoetin – a widely prescribed therapy with significant commercial value – were increased ten fold.

“The biologics industry has developed a number of protein expression systems with fully-optimised promoters and poly-A sequences, providing enhanced protein yields,” said Prof Nicholas Proudfoot, who’s group made the finding. “Improvements in this area have slowed to incremental yield increases, which has frustrated many in the industry.

“We discovered that the part of the protein-expression process know as termination – generally considered unimportant in increasing protein yields, is in fact a driving force for optimal gene expression.

“We identified a new location in the DNA sequence which turns out to play an extremely important role in the termination process. To date this method has been successful in providing this further ten-fold increase in protein production in a range of cell systems.”

The sequence is also in an area of the genome know as the “post poly-A”, and Proudfoot explained that this means the integrity of the protein expression sequence itself is well protected as no insertion of new sequences close to the actual protein sequence is needed.

The group remark in the paper that: “Our findings may have wide-ranging implications for in vivo protein production. This may be especially true in situations where efficient protein expression is difficult or expensive to achieve.”

The technology is broadly applicable to any application where protein is produced, either in the laboratory or at an industrial scale. It is being developed for eukaryotic systems but may be more widely applicable. Monoclonal antibodies and therapeutic proteins appear to be good initial applications.

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