Membrane proteins are important therapeutic targets as they transduce signals into cells, transport molecules, bind to surfaces, and catalyze reactions. However, researchers face challenges when developing antibody-based drugs targeting membrane proteins, such as monoclonal antibody and chimeric antigen receptor (CAR) T cell therapies, because the proteins are embedded within the membrane, leaving only a few surface-exposed epitopes accessible to therapeutics.
To discover potentially therapeutic antibodies, researchers employ antibody display systems where antibody fragment libraries are inserted into cells or phages that then “display” the proteins on their surfaces. Early display systems used microorganisms to express mammalian proteins. Newer mammalian systems improve upon bacteria, yeast, and phage display by producing antibody fragments via endogenous eukaryotic secretion machinery.1 This ensures that mammalian antibodies fold properly and are compatible with downstream mammalian cell production systems.
Typical mammalian display systems can only screen antibody libraries with up to 107 variants due to low transfection ...
