During the past decades, in vitro display technologies have opened up the possibility of interrogating large peptide or antibody libraries for the discovery of lead therapeutic or diagnostic candidates against a variety of antigens, in a relatively short time frame.
At IRBM, we have over two decades of experience with one of the most advanced display technologies, Phage Display, which is the paradigm of the genotype-to-phenotype linkage on which all the display technologies are based.
In Phage Display, the peptides or antibody fragments are displayed as fusions with one of the coat proteins of the filamentous phage M13. A phage library displays an enormous diversity of peptide or protein variants (109– >1010). In a screening campaign, those variants with high affinity and specificity to the target are isolated through iterative rounds of affinity selection. Then, the sequence of the positive binder variants is determined by sequencing the gene coding for the displayed peptides or proteins.
We can screen proprietary phage libraries displaying:
- Peptide libraries (complexity: 1 x 109)
- Antibody libraries (complexity: 3 x 1010)
We can also design and generate custom libraries that are best suited for the target of interest.
In the field of macromolecule discovery, the possibility to explore combinations of amino acid and/or binding determinants by rational design is often hampered by the lack of previous knowledge or by limitation in synthetic technologies.
The availability of the above mentioned libraries and the generation of target-specific libraries allows the identification of hit molecules to be further developed as therapeutics, diagnostics or tools for biology discovery. We can apply display technologies to the discovery of biologically relevant compounds, such as:
- Identification of peptides with improved receptor affinity for therapeutics development in IP free areas
- Identification of peptides with improved target affinity for PPI disruption for further development (e.g. through peptidomimetic approaches)
- Identification of antibody or antibody-like scaffolds for use in immuno-oncology.
The interplay between molecular biology, display technologies, testing and synthetic biology is key for the discovery of novel entities able to open innovative avenues toward unprecedented therapeutic approaches. At IRBM, we offer all these capabilities available under one roof.