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Published on: October 15, 2016
Design and validation of a novel GPCR antibody screening method based on tripartite fluorescence complementation
Yanan Wang1, Peng Xu2, Qin Chen3
1Department of Pharmacy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Biochemical and Biophysical Research Communications
|May 13, 2026
Summary
Researchers developed a novel method for screening G protein-coupled receptor (GPCR) antibodies using fluorescence complementation and phage display. This approach overcomes challenges in antigen stability and interspecies differences for developing new antibody drugs.
Area of Science:
- Biotechnology
- Immunology
- Pharmacology
Background:
- G protein-coupled receptors (GPCRs) are crucial drug targets in numerous physiological and pathological conditions.
- Antibody drugs targeting GPCRs offer enhanced specificity, longer half-life, and fewer side effects, driving significant research interest.
- Current development of GPCR antibodies faces hurdles including unstable antigen availability and interspecies homology issues.
Purpose of the Study:
- To establish a novel antibody screening approach for GPCR-targeting drugs.
- To overcome challenges related to antigen stability and interspecies homology in antibody development.
- To provide a new technical framework for the discovery of GPCR antibody therapeutics.
Main Methods:
- A combined approach utilizing fluorescence complementation technology and antibody phage display technology was developed.
- Cell-surface expressed GPCRs were employed as antigens to maintain native receptor conformation.
- In vitro screening via phage display was performed to bypass interspecies homology limitations.
- A tripartite split enhanced green fluorescent protein (EGFP) system was used for high-specificity detection.
Main Results:
- The novel screening method successfully preserved GPCRs in their native conformation using cell-surface expression.
- The in vitro phage display screening effectively circumvented interspecies homology challenges.
- The method's feasibility was confirmed using Mogamulizumab, a known GPCR antibody drug.
- High detection specificity was achieved through the use of tripartite split EGFP.
Conclusions:
- A novel and effective method for screening GPCR-targeting antibody drugs has been established.
- This approach addresses key challenges in GPCR antibody development, including antigen stability and interspecies differences.
- The developed technology offers a new platform and conceptual strategy for advancing GPCR antibody drug discovery.
