Synthetic biology offers a bonus for biologics April 28, 2017 Biologics pretty much sweep the leader board for money-making drugs globally. They are also excellent medicines, offering relief for millions of patients with chronic and often life limiting diseases. So what does synthetic biology have to offer this therapeutic success story? This was the question posed at a one-day event run by Innovate UK KTN and the Centre of Excellence in Biopharmaceuticals at the Manchester Institute of Biotechnology on April 26th What are biologics? The vanilla definition encompasses naturally derived molecules such as peptides, proteins and monoclonal antibodies. But today they come in a wide variety of more exotic flavours including antibody fragments, so-called bi- and event tri-specific antibodies, aptamers, drug-antibody conjugates as well as cell-based products including stem cell therapies and immunotherapies. Given that 2016 sales of biologics topped $160 billion, biologics don't see to be struggling as a therapeutic class. But the technology underpinning the production of biologics, mostly using Chinese Hamster Ovary (CHO, mammalian) or Escherichia coli (bacterial), is around 30 years old and showing their age. Indeed, industry argues that there is plenty of room for improvement in what is arguably still a ‘black box’ production system. By cell engineering and process optimisation there are gains to be made by lowering the cost of production, improving the stability of the cell production lines, improving the secretion of biologics from cells, and even the assessment of the activity and quality of the final product. For some of the more innovative biologics, which can be incredibly hard to express, solving this will be essential if they are to become commercially viable medicines. So the question is: Can synthetic biology help? In short the answer is yes. Indeed, the synbio research ongoing in the Rosser lab - including engineering safe landing pads into CHO genomes to optimise yield, deploying synthetic transcription factors to turbo charge cellular protein production and smarter ways to speed up selection of 'super' producers - will help. But synthetic biology alone is not enough if we are going to expand, explore and deliver the wide array of biologic-based therapies needed to address the 21st century challenges in human and animal health. Think rapid vaccine production for emerging infections, small batch ‘personalised’ immunotherapies or patient-stem-cell derived regenerative medicines; these will only be economically viable if we have robust, cost-effective and flexible production platforms. To achieve this step change in productivity, biologists will need to work closely with process engineers to translate strategies into robust production platforms. We will need to deploy all the tools we have for cell engineering from DNA design and assembly techniques, the whole gamut of 'omics technologies, and novel computational design tools that can predictably generate novel proteins functions. And then the hard part, getting the regulators on side to ensure we can get safe and effective products to where they really need to be – in patients. Bringing these diverse communities together to better understand their respective challenges is a great first step in a long journey. Dr Liz Fletcher, Center Manager Publication date 06 Jul, 2020
