Oxford: Precision for protein production

Licensing opportunity

Oxford researchers have developed a new technique to prepare proteins for use as therapeutic drugs. The technology, which Oxford says represents a significant step forward from current production methods, will enable the development of purer and more effective protein-based drugs.

Two papers on the technology have been published this year in the Journal of the American Chemical Society, and it has been patented by Isis Innovation, the University of Oxford’s technology transfer company. It is available for licence to commercial partners, who should contact Isis for further discussions.

Therapeutic proteins are currently prescribed for the treatment of cancer, heart attacks, cystic fibrosis, strokes, diabetes, anaemia and haemophilia. Many more protein-based therapies are in development for other diseases.

The new technology – developed by University of Oxford Professor Ben Davis – will allow drug developers to achieve “chemical post-translational modification”, a step in which carbohydrates, peptides, and other useful molecules are attached to proteins. Such modifications are vital for the manufacture of therapeutic proteins because they control the way that proteins are transported around the body, recognised by tissues, absorbed by cells, and eventually metabolised.

At present, therapeutic proteins, such as insulin (a hormone that controls blood-sugar levels) and erythropoietin (EPO, a hormone that controls red blood cell production), are produced using cell-based systems including bacteria, yeast or mammalian cells.  The cell systems attempt to mimic the way that proteins are produced in human cells.  However, the different biochemistry of the host cell systems means that they do not perform many post-translational modifications in an identical way to human cells. Hence there is strong need for new protein modification techniques which don’t rely upon host-cell systems and can take advantage of the control of chemistry.

“Using our new technique, cysteine, an amino acid, is converted to dehydroalanine,” said Davis. “Dehydroalanine provides a “chemical handle” in the resulting protein at which molecules, such as carbohydrates, peptides or polymers, can be attached. We hope that this technique will prove to be an important breakthrough in the development of better protein-based therapies.”

Using the Oxford technology, says Isis, it is possible to reliably and selectively produce specific formulations of therapeutic proteins. This means that the pharmacological behaviour of individual formulations can be studied and the most effective candidates can be selected for use in the clinic.

It may also be possible to design drugs so that they are only delivered to the organs or tissues that require treatment. Targeted therapies would require lower doses to be administered to patients, significantly reducing side effects.