Phage display
Phage display technology is based on the linkage between phenotype and genotype and on the replicative capacity of filamentous bacteriophage. Foreign DNA fragments can be inserted into filamentous phage genes codifying for phage coat protein to create a fusion protein that is displayed in the phage surface.
Billions of antibody fragment (Fab) sequences can be displayed on phage and presented to different type of proteins in various possible conformations to select specific monoclonal antibodies (mAbs).
Due to the flexibility of the phage display-based selection process, this technology enables the identification of monoclonal antibodies with very specific characteristics, representing an alternative to the classical hybridoma technology.
The phage display cycle for selection of Fabs
Features that differentiate phage display as an efficient technology for the isolation of mAb
|
Feature |
Description |
|
High throughput |
Entire library |
|
Selection for function |
Possibility of selecting antagonistic, agonistic, internalizing antibodies, etc. |
|
Broad range of epitopes |
Different strategies available to select for epitope specificity |
|
Selection for affinity |
Selection of monomeric and monovalent displayed Fab libraries on low concentration of antigen in solution drives the isolation of antibodies with higher affinity/potency |
|
Selection for stability |
Opportunity to isolate stability improved antibody variants by selecting at stringent conditions (phage is extremely stable) |
|
Selection for native conformation |
Selections on cells with low copy numbers of receptors is possible |
|
Well established technology for therapeutic antibodies |
Humira (anti-TNFα from Abbott / CAT) and Lucentis (anti-VEGF from Genentech), clinical products in the market, were obtained via phage display |
