Objective
The long term goal of this project is to design a production process for pharmaceutical proteins which includes an extended production phase in non proliferating cells. This highly innovative process will address major current industrial problems and will be based on creative application of recent developments in molecular genetics. In particular, the novel process to be created and demonstrated in this Project has clear potential to improve significantly both the quality of the pharmaceutical protein and the amount of this product obtained. This new process is based on genetic modification of CHO and BHK mammalian production cell lines so that cell proliferation can be restricted at a chosen point of the process, providing an extended interval of protein production with minimal cell growth. This should allow long-term, high- consistency product formation under technically and economically favourable conditions.
In separate but cooperating lines of research, two different types of control genes that interact in different ways with the cellular proliferation machinery will be introduced and conditionally regularly by the concentration of low-molecular-weight compounds in the medium. In one approach, expression of recombinant cyclin E, which activates proliferation in protein-free medium, will be repressed, resulting in restriction of further growth. Alternatively, proliferation inhibition will be accomplished by overexpression of an unusual tumour suppressor. Interferon Regulatory Factor 1 (IRF-l), which, unlike cyclin E, does not intervene with the cell cycle. Both of these novel proliferation control strategies will be evaluated in four specific systems: a CHO host, a BHK host, an industrial recombinant BHK cell line (B4B 1 from the Master Cell Bank of Novo Nordisk, producing Factor VII which is now in human clinical trials), and the CHO host transfected with an industrially-supplied expression vector for a pharmaceutical protein now in development for human use (s/ICAM from Thomas). The CHO and BHK hosts engineered for proliferation control will be further developed as expression systems by identifying promoters and other genetic elements which enhance productivity of growth-arrested cell. Basic studies of the physiology of all cell lines constructed in this project, including NMR studies of intracellular state, will be conducted, and suitability of these cell lines for extended, dense, stationary culture will be examined. Novo Nordisk will evaluate Factor VII production by proliferation-controlled B4Bl cells, and Thomas will produce s/ICAM using the proliferation-controlled CHO expression system constructed in this project. Both companies will characterize in detail the quality of the product, including glycosylation, made with these new systems.
The industrial significance of the concept to be developed and studied during this Project is evidenced by major commitments to the Project by two of the most important companies in Europe, Novo Nordisk and Thomas, active in protein pharmaceutical production and cell culture R&D. Although different in specifics because it is based on such recent discoveries? this project clearly embraces both the general goals and strategic approach desired for the EU Cell Factory programme.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences molecular biology molecular genetics
- medical and health sciences medical biotechnology genetic engineering
- natural sciences biological sciences biochemistry biomolecules proteins
- social sciences economics and business economics production economics productivity
- medical and health sciences basic medicine physiology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
38124 BRAUNSCHWEIG
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.