The biotechnological use and further development of phage display

Información del proyecto

Identificador del acuerdo de subvención: BIO4960389

Proyecto cerrado

Fecha de inicio 1 Octubre 1996

Fecha de finalización 30 Septiembre 1999

Financiado con arreglo a

• Specific research, technological development and demonstration programme in the field of biotechnology, 1994-1998

Coste total

Sin datos

Aportación de la UE

Sin datos

Coordinado por

Scuola Internazionale Superiore di Studi Avanzati
Italy

Objetivo

Phage display is a relatively new technique which involves the expression of peptides or proteins on the surface of phage as fusion proteins attached to normal phage proteins. The coupling of a protein on the surface of a phage with the gene which encodes it within the phage allows a rapid evolution of protein properties on the basis of their binding or (in some cases) catalytic activity, by a series of recursive cycles of phage binding, elution and amplification. This technique started with the exposition of peptides, used initially to identify monoclonal antibody epitopes and subsequently the binding sites recognized by other proteins, and has since progressed to include the exposition of a large number of known proteins. One of the most successful applications of phage display has been the relatively easy derivation of monoclonal antibodies against many diverse antigens using large phage antibody libraries, and the subsequent improvement of the affinity of selected antibodies by their mutation and further selection. The improvement of the binding affinity of hormones to their receptors (e.g. growth hormone) have also been carried out using phage display. Following the display of variants of known proteins, elegant methods have now been developed to produce cDNA libraries displayed on phage where selection of unknown proteins can be made on the basis of their binding properties.
Most methods used for selection have usually been physical in nature. However, recent developments have attempted to exploit the biology of the phage by coupling selection with infection, a selection method which is likely to be very powerful if it can be fully developed.
The importance of phage display as a new industrial tool is demonstrated by the large number of American (and latterly European, some included here) biotechnology companies which are now using this technique to provide either leads in the development of new drugs, or to create new protein based drugs based on antibodies or peptides.
The objectives of this large concerted action are to bring together most of the groups in Europe actively using, or developing improved, phage display methods. By regular meetings and lab visits it is expected that reagents will be exchanged and exciting developments in this field will be rapidly communicated to the European 'phage display community', so providing a collective benefit and competitive advantage. Specific research objectives can be grouped into the following areas:
A. Improvements in the quality of antibodies selected using phage display by increasing the size and quality of the libraries, by improving the antibody frameworks so that they are better expressed on phage, and by developing mutati and selection methods which improve the affinity of phage antibodies once initial binders have been selected.
B. The improvement of selection methods, including the development of biological methods of selection ('selection by infection') and the development of selection methods which permit the isolation of phage antibodies specific for a particular diseased or physiologically altered tissue.
C. The use of phage display to select specific antibodies or peptides which recognise proteins of medical or commercial interest.
D. Improvement of vectors used in phage display.
E. The further development of techniques which permit the cloning of cDNA on phage.
F. The development of novel applications of peptide phage libraries by the creation of libraries which are either modified (by e.g. phosphorylation) or constrained, or by the isolation of peptide phage which are specific for particular diseases.
G. The use of phage display to alter the properties of proteins of medical or commercial interest.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › microbiología › virología
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › proteínas
• ciencias naturales › ciencias biológicas › genética › mutación

Programa(s)

• FP4-BIOTECH 2 - Specific research, technological development and demonstration programme in the field of biotechnology, 1994-1998

Tema(s)

• 0601 - Structure-function relationships

Convocatoria de propuestas

Datos no disponibles

Régimen de financiación

CON - Coordination of research actions

Coordinador

Scuola Internazionale Superiore di Studi Avanzati

• Aportación de la UE: Sin datos
• Dirección: Via Beirut 2/4 ; 34013 Trieste ; Italia
• Coste total: Sin datos