Researchers develop new technique for developing drugs to treat serious illnesses

Published: 15-Nov-2013

International team led by Leicester University exploits the power of evolution to create designer proteins

Researchers in the Department of Cardiovascular Sciences and Department of Biochemistry at the University of Leicester, UK, together with colleagues in Cambridge, US and Italy, have employed a new technique to create protein-based drugs potentially to treat a range of illnesses.

Lead researcher Professor Nick Brindle, says this technique harnesses the power of evolution to engineer specific functions into a protein, such as the ability to neutralise a toxin or to activate healing.

'This involves making a particular cell type generate millions of different variants of our protein, selecting the variants that have improved properties and then repeating the cycle until the protein has been changed to a form with the exact properties we want,' he says.

To show how the method works, the group took a protein normally found in the body and evolved it into a form that can block a molecule involved in blood vessel growth and inflammation.

Called a ligand-trap, this new protein is now being developed as a potential therapeutic for treating heart disease, inflammation and other illnesses.

This new approach promises to make engineering of such proteins not only possible but also relatively easy

'The idea that you can evolve proteins into forms that do what you want is not new, but it has been very difficult to do this for many of the complex proteins that we want to use as drugs or for other applications,' added Brindle.

'This new approach promises to make engineering of such proteins not only possible but also relatively easy. In addition to medicine, these specifically evolved ‘designer proteins’ have a wide range of applications in the chemical, pharmaceutical, and agricultural industries.

'This is a big step forward. We are hoping that, over the next five years or so, this new protein can be developed into a form that could be used to treat inflammation and other conditions.'

The work, published in the Journal of Biological Chemistry, was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), MRC and the Wellcome Trust. The Leicester team collaborated principally with Dr Julian Sale at the MRC Laboratory of Molecular Biology in Cambridge, with additional input from Dr Hiroshi Arakawa in Italy and Dr Jean-Marie Buerstedde at Yale.

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