Public Funding for Askbio UK Ltd

Production of biopharmaceuticals that are toxic or have detrimental effects on the growth of the host cell line is very challenging. To overcome this challenge researchers have developed a number of promoters allowing control of protein expression during the bioproduction process. The primary aim of that research was to enable a 2-step bioprocessing platform to be developed whereby the expression of the gene of interest is switched on after sufficient biomass has been obtained or a gene that has negative effects on DSP or product quality can be silenced. This type of process is particularly attractive for the production of difficult to express or toxic proteins where expression is deleterious to the cell or where host cell protens co-purify with the final product and complicate purification strategies. However, to date these promoters have proven to have insufficient control for the task with leaky expression observed or the need for multiple rounds of transfection and cell line selection to achieve the requisite control. Ideally the activity of those promoters should be inducible/repressible by a stress stimulus (chemical or physical) during the production process and allow tight control over the expression levels to ensure maximum productivity and high quality of the final product. To this end Synpromics has used its proprietary technology to develop new synthetic inducible/repressible systems that have demonstrated exquisite control of gene expression. These systems offer significant advantages over the currently available systems as they are small in size, can be driven from one plasmid, offer fine tuning of gene expression, are driven by physiological or chemical stimulus that are non-toxic and are therefore ideal for improving productivity and minimising costs during bioproduction in CHO cells. Using these novel gene expression control tools Synpromics and Lonza will embark on an 18 month exemplification program to validate the use of these control tools in a GMP environment using well characterized model proteins. Once validated in an industrially relevant situation, these tools will then be used to design a process for a therapeutic construct and a manufacturing process will be developed. In addition to this outcome, the validation of Synpromics's control tools will increase the flexibility of bioproduction and offer the industry new powerful tools with which to increase the number and type of proteins that can be produced from CHO cells.

Evolving therapeutic approaches of cell and gene therapy are harnessing the power of viruses in order to modify genomes of cells to produce a therapeutic effect. Such therapies are starting to show efficacy in the clinic, but one of the key challenges to their widespread use is the ability to make large quantities of virus at a low cost. This project seeks to address this challenge by creating new methods of producing large quantities of virus at a low cost. It brings together Synpromics, a synthetic biology company based in Edinburgh, and the Cell Therapy Catapult, one of the UK’s network of Catapult centres focused on developing and growing a cell and gene therapy industry in the UK.

The bioscience industry currently relies on a small number of organisms to produce the majority of the recombinant products on the market. A collaboration between two UK synthetic biology Synthace and Synpromics and University College London, this project combines cutting edge computational techniques with multifactorial experimental design to develop a novel toolset that will allow the rapid bootstrapping of novel chassis organisms for synthetic biology. This will enable future processes to use chassis that are far better suited to the industrial conditions they are used under, and accelerate the use of synthetic biology in healthcare, food production, chemicals and energy. Outputs of the tools will be fully characterised to ensure they are fully robust under a range of conditions, making sure that they will be of maximum use to the synthetic biology industry

The collaboration between Synpromics Ltd. and Touchlight Genetics Ltd. will combine two highly innovative and complementary technology platforms to develop an improved approach to developing DNA vaccines. The project will leverage Synpromics's proprietary technology to rationally design synthetic promoters that drive cell-specific antigen expression and that enhance the effectiveness of Touchlight Genetics’s unique synthetic DNA vaccine cassette platform. The resulting new technology will subsequently be applied by Touchlight Genetics in the company’s internal DNA vaccine develoment programs, as well as be available for licensing by other developers. The project is expected to establish a unique UK-based synthetic biology capability for the production of safer and more effective DNA-based medicines.

The collaboration between Synpromics and Ingenza is focused on developing proprietary protein production systems in engineered yeast strains that improve on currently available alternatives by incorporating novel synthetic promoter constructs rationally designed to drive optimal gene expression. The enabling technology that the project aims to deliver will address significant limitations faced by a wide range of bio-manufacturers using yeast-based expression, enabling the more efficient production of protein products and intermediary production enzymes. The combination of Synpromics's and Ingenza's innovative technologies and expertise is expected to validate a platform on which to build an even broader range of solutions to yeast-based expression challenges, thereby establishing in the UK a leading capability in synthetic biology and sustainable industrial bioprocessing.

Enhancing methods of protein expression is fundamentally important to new drug development and the efficient production of biopharmaceuticals. The consortium aims to develop a novel means of designing and constructing synthetic promoters that can be employed on an industrial scale to drive the expression of proteins for commercial applications. This will be achieved by combining the synthetic promoter design capabilities of Synpromics with improved DNA assemble methodology from Genabler and systems biology expertise from the SynthSYS institute of the University of Edinburgh. The project will yield a novel platform technology that can be used to create synthetic promoters with multiple applications across the biotech sector. This initial feasibility study will incorporate disparate expertise from the three partners to construct synthetic promoters that can enhance the production of proteins in mammalian cell culture systems, with a view to improve upon protein yield and quality.

The project will deliver new tools that can be used to test potential new drugs, food constituents with possible health benefit, and which also offer a new approach to measuring the effect on human health of particles present in our domestic or workplace environment. These tools will be based upon living cells that are placed in situations where they reproduce the function of the lung or the digestive tract surfaces. To measure the response of these cells to challenge by the test materials, the project will, as one of its prime objectives, introduce reporting systems into the cells that allow their state of health and functions to be measured without disturbance, over the duration of an experiment. The proprietary techniques for introducing these reporters will be a prime focus of the project, as will the new cell models that are used to demonstrate the power of the combined technologies. The project outputs will have wide application across the pharmaceutical, food and other industry sectors.