GPCR (G protein-coupled receptor) protein is the most abundant membrane protein in human genome, its main function is to transmit the extracellular information into the cell through the signal pathway, and then cause a variety of cell responses. One third of the drugs on the market target the GPCR protein, activating or blocking the GPCR signal pathway to achieve therapeutic effects. Compared with small molecule drugs and antibody drugs of extracellular proteins, antibody drugs of GPCR can not only activate or block the signal pathway, but also directly eliminate diseased cells through the ADCC or ADCP effect of antibodies in a targeted way.
In the past, the progress was slow due to the difficulty in antigen preparation and the lack of high-throughput screening methods for GPCR antibody discovery. However, with the rapid development of antibody development technology, Biocytogen has been equipped with a perfect GPCR antibody discovery platform.
Advantages of Biocytogen’s GPCR platform
1. Antigens with native conformation: In order to be able to scientifically and comprehensively evaluate the druggability of targets and screen for antibodies with different binding epitopes and physiological functions, Biocytogen insists on immunization of mice with antigens with intact native conformation. GPCR antigens are provided to RenMiceTM mice by means of DNA immunization and cellular immunization, ensuring that the fully human antibodies obtained are highly specific and diverse.
2. In vivo DNA transfection technology: In order to further improve the effect of DNA immunization, Biocytogen selects suitable transfection adjuvants in combination with different injection methods based on numerous experimental data to improve the efficiency of in vivo transfection of DNA, and improves the expression level of GPCR antigens in mice by optimizing the plasmid element.
3. Immunopotentiating peptide: Fusion of a short peptide fragment that effectively binds to mouse MHC class II molecules to the intracellular C-terminal domain of GPCR enhances the immune response in mice by activating CD4+ T cells.
4. Knockout mice and humanized mice: Biocytogen uses target gene-knocked out RenMice, for antibody discovery. Compared with non-knockout mice, the knockout RenMice produce antibodies that identify the antigen sequences that are identical in mice and humans, turning the intrinsically minimal extracellular domains of the GPCR targets entirely into recognizable epitopes. The use of knockout mice not only improves the diversity of epitopes recognized by antibodies, but also results in more antibodies cross-recognized in humans and mice, which facilitates efficacy validation in mice. Many GPCR targets have low homology between humans and mice, making it difficult to obtain antibodies cross-recognized in humans and mice. For these targets, Biocytogen has bred target gene-humanized mice or mice humanized for both the ligand and receptor to provide suitable experimental animal models for the targets where cross-reactivity antibodies are difficult to obtain.
GPCR Antibodies under Development
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