Currently, developing antibodies that target multi-pass transmembrane proteins (such as GPCRs, SLCs, and ion channels) is a pain point in the field.

There are currently two common approaches of preparing membrane protein antigens:

1.First, water-soluble segments of a membrane protein are prepared as antigens of the protein.

2. Second, a vector encoding the target protein is delivered into cells, so that the target protein can be expressed on the cell surface.

Unfortunately, the three-dimensional structures of the antigen segments prepared by the first approach may significantly deviate from the structure of the full-length antigen. Therefore, antibodies obtained from this approach are defective in therapeutic value even if these antibodies show positive signals in Enzyme-Linked ImmunoSorbent Assay (ELISA).

The antigens prepared by the second method are disadvantageous for their unstable surface expression. In addition, cell surfaces are “noisy” due to the presence of many other surface proteins, thereby resulting in false-positive antibodies.