Ciloa offers a highly advanced tool for developing new drugs, monoclonal antibodies, vaccines, diagnostics and new kinds of therapies.
The antigens used to develop monoclonal antibodies that recognize conformational epitopes must exhibit fully native conformation. At the same time, the native conformation of receptors is required for recognition by their natural ligands or by drugs interfering with their functions.
The folding conditions for water soluble proteins have been well established in the scientific community at this time. On the other hand, proper folding is challenging to obtain for integral membrane proteins, which are present in a heterogeneous environment.
Several additional conditions are required for folding, including glycosylation, multimerization, proteolytic cleavage, and phospholipid membrane environment. As the precise combination of all of these factors is crucial for eukaryotic cells, they dictate the use of a specific mechanism with the corresponding enzymes, chaperones, and strict quality controls in order to produce native membrane proteins with their post-translational modifications.
The scientific community is well-aware that these specific constraints can be satisfied for human membrane proteins only by expression in human cells, or at least in animal cells. Therefore, most human membrane proteins produced either synthetically, by E.coli, yeast, or insect cells cannot present a fully native conformation. When membrane proteins produced in human cells are detergent-extracted, to be subsequently reintroduced in liposomes, they can lose their native conformations.
Get ready for a change
Until now, the best source of structurally native membrane proteins for the development of antibodies has been whole cells expressing these proteins, or membranes purified from these cells. Unfortunately, the low concentration of membrane proteins and the high amount of other proteins are major drawbacks for developing strong and specific immune responses.
Similarly, the screening of drugs recognizing receptors is hampered by heterogeneity, the lack of stability, and the backgrounds of cellular responses.
A source of truly native membrane proteins, naturally secreted at high concentrations outside cells, can dramatically improve the development of monoclonal antibodies specific to conformational epitopes as well as the development of drug leads.