Harnessing mRNA Immunization Strategy for Challenging GPCR Protein Antibody Discovery

Multi-transmembrane proteins, especially G-protein coupled receptors (GPCRs), are extremely difficult to develop antibodies against due to their low expression levels, insolubility in vitro, unstable purification and difficulty in maintaining their native conformation, which has greatly hindered the development of antibody drugs against GPCRs.

In this webinar, the speaker will discuss the use of mRNA as a brand-new antigen format for antibody development targeting transmembrane proteins. The mRNA-expressing target protein could be delivered in vivo through lipid nanoparticles (LNP), where the translated antigen directly stimulates the immune response in the host.

In this way, complex and tedious antigen extraction and purification steps in vitro could be completely avoided, greatly simplifying the GPCRs’ antibody production process. Next, mRNA immunization could be combined with traditional hybridoma fusion, B cell cloning or Beacon single B cell sorting platform for positive B cell screening to develop mouse/rabbit monoclonal antibodies.

R&D and production data showed that multiple transmembrane proteins could be custom-designed into mRNA for successful immunization with inspiring serum titer after two doses. In comparison with the traditional immunization strategy, the monoclonal antibody developed from mRNA-LNP immunization exhibited higher affinity and probability of recognizing/binding to natural antigens than protein, DNA or cell line immunization. Furthermore, mRNA-LNP immunization for antibody production could also be applied to other types of proteins, including secreted proteins, bacterial proteins and protein fragments.

Register for this webinar today to understand how an mRNA immunization strategy opens a new avenue in the antibody production of difficult protein targets and accelerates the development of antibody drugs against difficult-to-express targets.

Speaker

Dr. Tingting Xiao, Antibody Senior Scientist, GenScript

Tingting Xiao graduated with a PhD degree from the University of Hong Kong in August 2022. She has authored four impactful papers in esteemed SCI journals, with three securing a coveted Q1 ranking and one in Q2 under her leadership as the first author. Dr. Xiao joined GenScript as a Senior Scientist in October 2022 and is currently responsible for the development of multiple transmembrane protein antibody development projects and the optimization of the antibody sequencing platform. She has now delivered CLD18.2, CCR9, CCR8, CXCR6, PTGER4, ACHA9, Col10a1, truncated Her2 and IGMDE antibodies using the mRNA immunization platform. Dr. Xiao’s innovative contributions exemplify her commitment to scientific advancement and position her as an important figure in antibody development.

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