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Improved nanobody using a yeast display system
One of the aims of the project of our team is to develop low-cost protein therapy for rare bleeding disorders using single domain antibody fragments (nanobodies). Nanobodies have several advantages, including a low (if any) immunogenicity when applied to humans. Further, their small size (±17 kDa) facilitates their molecular engineering.
We obtained by immunizing a llama with our target of interest, a nanobody that has demonstrated in in vitro and in vivo experiments its ability to improve a rare haemorrhagic phenotype.
Fusions to the C-terminal end of the Aga2p mating adhesion of Saccharomyces cerevisiae has been used in many studies for the selection of affinity reagents by yeast display followed by flow cytometric analysis. Here, thanks to the expertise of Hybrigenics and using an improved yeast display system for the screening of nanobody immune libraries, we have been able to obtain a variant of our nanobody of interest with an affinity improved 50 fold compared to the molecule of origin. This variant has kept all its therapeutic potential and is now one of our lead product in our pipeline of products in pre-clinical stage. — Dr Olivier Christophe (INSERM U1176, Le Kremlin Bicêtre, France) - Europe