Isogenica: manufacturing better proteins for industry
Producing enzymes, proteins and other complex molecules is one of the backbones of the modern multi-billion pound molecular biology industry. Pharmaceutical companies use these products for everything from clinical trials to validating drug targets.
Dr Anna Hine and colleagues from Aston University successfully commercialised an innovative and elegant technique for building better proteins from gene libraries. They licensed the technology to protein engineering company Isogenica in 2010, which now markets it as COLIBRA, a tool for developing antibody-based therapies.
“It makes protein engineering companies do a far better job, which in turn should lead to better biopharmaceuticals,” says Hine. “And it's already led to biotech employment in the UK.”
|$140Bn||Annual value of world market for biopharmaceuticals; of which antibody therapies at least $40Bn|
|25||Number of full-time employees at Isogenica; about one-third are involved in activities utilising COLIBRA|
|>30||Number of custom DNA/protein libraries made for biotech and pharmaceutical companies since licensing the technology in 2010|
Increasingly, antibody-based therapeutics, generated and optimised in the laboratory, are replacing small, chemical drugs as a way to treat many very serious conditions from rheumatoid arthritis to cancer. An example of such an approach is Herceptin which is used in the treatment of certain types of breast cancer. Because of their exquisite specificity to drug targets, antibodies will also form a key component in advances towards ‘personalised medicine’.
It started with Hine’s interest in zinc-finger proteins, important structures that bind to and interact with DNA. She realised soon that this BBSRC-funded research in 2001 would have reach beyond zinc fingers. They used BBSRC Follow-on Funding in 2005-06 which helped her colleagues Dr Marcus Hughes and Dr Mohammed Ashraf (then a PhD student) to develop ProxiMAX randomisation.
ProxiMAX gets around the fact that some protein's amino acids are encoded by up to six codons [triplets of three DNA bases] and others by only one. Because of the huge numbers of combinations of DNA that can encode different proteins means you end up with enormously skewed DNA libraries. This bias becomes a problem during the nitty-gritty work of manufacturing complex proteins: they come out at different concentrations and the screening technology to sort them works on the basis that all proteins are at the same concentration.
“Our invention got rid of the bias and the excessive size so we're just using 20 codons to encode 20 amino acids with no wastage,” says Hine. This means that companies that use this technique to make new therapies and test them can do so more simply, cheaper, accurately and efficiently.
The work led to Hine being awarded the BBSRC Innovator of the Year award in 2013; read a longer Q&A about her work.