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Development of efficient cellular systems for industrial production of human recombinant collagens to be used as biomaterials and in oral tolerance

Objective



Of the 19 known types of collagen, commercial use is presently limited to type I collagen used as biomaterial and type II collagen used as a therapeutic, because only these collagen types are readily available from animal tissues, and no human sources exist. Collagens can be used as components of medical devises, in injectable form, and in drug delivery. A new field of application is oral administration of collagens in certain autoimmune diseases, such as rheumatoid arthritis.
Despite the obvious need for recombinant human collagen, production of recombinant collagen with cost-effective expression systems, such as insect cells, yeast or bacteria, have been hampered by the complex post-translational modifications required for production of collagens.
The objective of the proposal is the development of cell lines of industrial importance, namely insect cells and yeast, to allow expression of native-like triple-helical recombinant human collagens.
As a result of co-expression of human collagens and human prolyl 4hydroxylase, the key enzyme of collagen synthesis, we have successfully produced large quantities of native-like triple-helical human type II and III collagens in insect cells. Furthermore, our results suggest that by using the multi-gene expression approach it will be possible to modify yeast to produce even higher amounts of human collagen. The application combines an integrated approach by academic and SME partners to further develop means of producing cost-efficiently in large-scale any human and animal collagens using recombinant technology, and to evaluate the properties of the produced recombinant collagens in order to allow selection of the most suitable production system for the various collagens and to understand the biological diversity of the them. A single group could not set up the proposed range of expression systems, nor could a single group assess all the qualities of the produced proteins. Therefore, comparison of these several expression systems is only possible as a joint, task-oriented venture between the different partners of this proposal.
Several problems can be circumvented by the recombinant technology; it will be possible to produce in unlimited quantities any type of collagen with important functions, but occurring in trace amounts or in insoluble form in tissues, thus enabling full exploitation of the biological diversity of the members of the collagen family; avoidance of genetic differences posed by administration of nonhuman collagens found to cause allergic reactions in some patients, and improvement of efficacy in applications requiring immune response, and; the avoidance of health risks in the form of viruses and prions. Thus the application will lead to the development of safe, reproducible and sustainable bioprocesses, which will increase the health of the population, and to the creation of new job opportunities in Europe.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

University of Oulu
Address
52 A,kajaanintie 52 A
90220 Oulu
Finland

Participants (4)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
7,Passage Du Vercors 7
69367 Lyon
FibroGen Europe Oy
Finland
Address
11,Kiviharjuntie 11
90220 Oulu
KAROLINSKA INSTITUTE
Sweden
Address
9,Doktorsringen 9 A
171 77 Stockholm
Max-Planck-Gesellschaft zur Förderungder Wissenschaften e.V.
Germany
Address
18A,am Klopferspitz 18A
82152 Martinsried