A more comprehensive off-target screen
Human cell microarray technology has long been the leading tool for assessing potential off-target binding against human plasma membrane proteins. However, off-target binding to secreted proteins also has the potential to cause clinical toxicity or alter the pharmacokinetic profile of biotherapeutics in development. As such, Retrogenix has adapted its technology to accommodate secreted proteins, creating a more powerful screen whilst maintaining a robust, high quality platform with a low rate of false positive results.
Tethering secreted proteins
As secreted proteins are not naturally localised on the cell surface, novel cDNA constructs have been developed which result in expression of ‘secreted’ proteins fused to inert transmembrane and intracellular domains. As these proteins are tethered to the membrane, binding can be detected using the same workflow as the plasma membrane library. Extensive testing and validation work has confirmed that binding of known ligand:secreted protein pairs could be identified consistently.