SELECT EXpress

We require effective means to produce proteins and protein-based complexes for use as therapeutics, as diagnostic reagents and to study fundamental biology. The structure of many of the products that would be desired (e.g. antibodies, growth factors) undergo modification during their passage through the secretory network in mammalian cells. In most cases, the modifications are essential for function and, in the case of products to be used as therapeutics, to prevent inappropriate immunogenic reaction. For this reason, higher eukaryotic cells are used as expression factories/platforms directed by engineered recombinant gene sequences to synthesize the desired protein product. The Chinese hamster ovary (CHO) cell is the basis of industry-standard systems allowing large scale production and such systems have been used to make marvellous breakthrough meedicines (biopharmaceuticals). In addition, to "standard" antibodies being used as therapies for various immune diseases and cancers, we are seeing the power of innovation proposing novel format biopharmaceuticals such as antibody-drug conjugates, multi-specific antibodies and domain-engineered proteins. With innovative ideas, the entrepeneurial researcher needs access to expression platforms that enable the production of sufficient product to undertake initial functional studies and ideally, for potential therapeutics, phase 1 clinical trials.

Academics and SMEs who discover most novel biopharmaceuticals, often cannot access industry-standard expression platforms due to the restrictive access and onerous commercial terms. The high cost and time required to develop an expression system can inhibit speed to market of those innovative new companies developing biopharmaceuticals. These restrictions can more generally delay scientific progress that is intended to enable improvements in human health. Therefore, the primary aim of this project is to develop an innovative, industry-leading, open-source expression platform with flexible, open-source license terms. This will drive significant academic and industrial uptake of the technology, generating revenue through sales of consumables.

Background work in the Dickson lab has identified a metabolic target that will enable the development of a new expression platform based around that metabolic selection marker, coupled with a specific (engineered) CHO cell line and matched media formulations. The system offers all the power of the current industry-standard platforms but has a greater stringent selection over cell health. This will enable a rapid and clean isolation of the desired recombinant clones and, by the nature of the metabolic selection, will enhance cell growth resulting in selection of greater numbers of recombinant clones, higher biomass in culture and improved overall cell performance as a platform for production of biopharmaceuticals in particular. Essentially, he basis of the particular metabolic marker means that the system also has the potential for application to severa;ll mammalian cell types not just CHO cells.

Towards commercialisation of the platform, this project will; generate key components and proof-of concept of the overall technical package, involving genome engineering to generate the specific CHO cell line that will be central to the platform. BBSRC support will also be used to build the (prior-designed) expression vector and to test specific media formulations that will form the culture selection, matched with cell line and vector.

In planning the route to commercialisation, we have built a team that includes an external partner who has extensive experience in commercialisation in the area of biopharmaceutical development. During the period of requested funding, we, as a team and with the support of the University of Manchester Innovation Factory, will work to build the results into a technical package and move towards launch of a start-up company.