Synthetic Biology Platform for CHO Cell Engineering

The process of CHO cell factory development still relies upon the widespread use of a very limited set of complex, functionally ill-defined genetic components (such as viral promoters) and trial-and-error screening to identify cells with desirable manufacturing characteristics. These processes are entirely incompatible with MedImmune's requirement to produce and test a diverse portfolio of next-generation biopharmaceutical products that are non-natural, engineered protein formats (such as bispecific MAbs and other fusion proteins) with unpredictable manufacturability. To enable both significant reductions in development times and significant improvements in production yields for these new products, there is an urgent need to shift from screening-led to design-led technologies; embedding prediction and design of product manufacturability at an earlier stage in bioprocess development to speed products into the clinic. Enabling technology that permits us to employ the core concepts underpinning synthetic biology (standardisation, design, prediction) to the development of next-generation biopharmaceutical manufacturing systems does not currently exist. It is vitally important that this is developed: We need to eliminate the current concept that some products are "difficult-to-express" (DTE), replacing this with the concept that a "designer product" requires a "designer cell factory" that does not rely on screening natural biological variation for functionality. Biomedicine development should not be limited by manufacturing technology, but by the ability of biomolecular engineers to design new, potent molecules. To make CHO cell factory synthetic biology a reality, it is necessary to design and test new genetic systems for cell engineering from the ground-up. In this project we will develop a synthetic biology platform for CHO cell engineering that will permit us to create bespoke synthetic CHO cell factories, harbouring multiple genetic components operating at optimal designed stoichiometries, capable of performing complex manufacturing functions that are currently not possible. This will enable both (i) reverse engineering of existing stable cell factories to render failed products manufacturable and (ii) forward engineering of new cell factories and products with predictable manufacturing properties.