Novel Method for Enhancing Protein Yields in the Lab and in Large Scale Manufacture - Isis Project No 3776
Isis Innovation, the technology transfer arm of the University of Oxford, releases a new method for increasing protein production. The technology has been validated for mammalian systems but is expected to be more generally applicable. EPO yields have been increased 1000% and this finding has been confirmed in two cell lines.
Promoters are required for protein expression and their “strength” usually correlates with the level of protein obtained. Other RNA processing signals within the gene (such as splice sites and polyadenylation sequences) have also been manipulated to enhance expression. Sequences beyond the gene have not been investigated for properties that enhance protein expression and their potential is untapped.
The technology is broadly applicable to any application where protein is produced, either in the laboratory or at an industrial scale. The technology is being developed for eukaryotic systems but may be more widely applicable. Monoclonal antibodies and therapeutic proteins appear as good initial applications.
The Oxford Invention
Oxford researchers have discovered DNA sequences which play an important role in transcriptional termination of RNA polymerase II. Inclusion of these sequences into a range of expression systems leads to increased levels of both mRNA and protein. An early example shows that expression of the commercially valuable erythropoietin (EPO) protein can be increased by at least an order of magnitude. This finding has been confirmed in two mammalian cell systems. This technology has the potential to be a valuable tool for individuals or companies that seek to enhance the yield of their chosen protein. Advantages of the Oxford ‘termination sequences’ include:
- Post poly-A sequences are a simple and low-cost technology.
- Their implementation is simple and only requires them to be cloned beyond the gene of interest.
- Once cloned, there is no extra cost beyond that normally required for standard protein expression.
- As the sequence is post poly-A, no alteration of the coding sequence is made, thus protein integrity is assured and unchanged.
- Early data suggest the magnitude of the effect can be very large – 1000%.
The Oxford invention is the subject of a patent application. Isis would like to talk to companies interested in developing the commercial opportunity. Please contact the Isis Project Manager to discuss this further.