A platform for the optimisation of metabolic pathways for glycosylation to achieve a narrow and targeted glycoform distribution

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Recently, the development of treatments for new disease has shifted away from traditional chemical compounds and towards protein therapeutics (biopharmaceuticals) like antibodies for the treatment of cancer and hormones for chronic diseases. Nearly 70% of these protein therapeutics have sugar molecules attached to them naturally which affect their function and how long they remain in the body. Because the sugars are so important for the drug function, one of the biggest problems in their manufacture is how to control what sugars are added (glycoform) and to ensure that all the proteins produced have the same sugars on them (homogeneous glycoform profile). Current production methods yield a non-homogeneous mix of glycoforms. Also, different glycoforms interact with the immune system in different ways, so it would be of benefit to be able to produce certain glycoforms over others depending on what the drug is and how it is meant to function. Our goal is to develop technology to rapidly determine the effects of different production methods on which glycoforms are produced and how homogeneous the glycoform profile is. To do this we will develop proteins which are produced inside the cells that are also producing the biopharmaceutical that report the concentrations of nutrients that are already known to influence glycoforms. Alongside, we will develop a computer model of the metabolism of the cells which can predict which glycoforms are produced. Using these two together, we should be able to design new media for the cells to use that result in a more homogeneous glycoform profile which we can change based on what the cells are fed with. We can also suggest genetic changes to the cells that would further help us produce a single, designed glycoform. This could lead to the production of drugs that are safer and require lower doses because they have a single glycoform attached which is the most appropriate for the function of that drug.