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Content archived on 2024-04-30

Development and automation of a method to select and produce phage-display antibodies to peptides

Objective



The Human Genome Project recently has produced nearly a million different Expre ssed Sequence Ta (ESTs) for which often no functional proteins are known. To us e this information there is an urgent need frc industry as well as from non pro fit organisations, for new technologies to link the DNA information to t functi onal protein expression. It is attractive to use protein fragments or peptides encoded by these sequence and in particular antibodies to these products, to st udy the expression and biological activity of the products. However, the curren t technologies to make anti peptide antibodies involve animals, are time a, mon ey consuming and, since for each peptide antibody one or several animals are ne eded, are not suited large scale automation. Recently a new technology, antibod y phage display, was developed, that makes possible to select and produce antib odies completely in vitro. The method is now generally used to deri antigen spe cific antibodies, provided pure antigen is availabe; this had not extensively b een applied peptides yet. It is with this phage display method that we would li ke to address the issue of generati thousands of anti peptide antibodies. O bjectives This project aims to combine the use of peptides as antigens and t he use of very large phage antibody librari to derive fast, in an automated fas hion, peptide specific antibodies, which may than be used f biotechnological or medical research, for diagnostic applications and as starting material for imm unotherapeutics. We will use a universal, naïve human Fab library containing ov er 10'° different antibody fragments and made by partner A2 in our studies. The first goal is to find the optimal conditions forcoating and presentation of th e pep tides to the antibody library. Next, the new technology will be compared to the currently used methodology (immunization of rabbits or mice) and optimi sed. To commerialize the system, we will automate the selection procedures and develop the most optimal format f production of the antibody fragments. These p rocedures should therefore yield a virtual 'selection machin which may be used for the rapid derivation of multiple peptide specific phage antibodies. Appl ications The different SMEs will validate the technology after completion of this 2 year research project in differe areas:
cumstomer designed anti peptide phage antibody service, research tools to identify new tum antigens, developme nt of diagnostic tests and starting leads for immunotherapeutics. This will req uire anoth 2 years after completion of the project. The successful development of the technology described in the proposal will have a major impact on researc h and technology development, in particular on the analysis novel gene or EST d erived products. The antibodies may be used to study the expression of the prod uct, purify the native gene product, to block the biological function of the pr oduct, and to validate the product certain medical applications.

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Call for proposal

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Coordinator

EUROGENTEC BEL S.A.
EU contribution
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Address
Parc scientifique de Sart-Tilman
4102 OUGREE
Belgium

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Total cost
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Participants (6)