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Abstract: Developing antibodies targeting native epitopes of multi-pass transmembrane proteins like GPCRs is challenging, spanning immunization, screening, and quality control. This abstract highlights two innovative strategies: engineering GPCRs within VLPs (virus-like particles) and nanodiscs. VLPs maintain native GPCR conformation, inducing robust, long-lasting immune responses. GPCR nanodiscs enable high-throughput screening and in vitro assays, exposing both extracellular and intracellular GPCR domains. This research explores diverse immunization protocols and screening methods through insightful case studies.