G protein-coupled receptors (GPCRs) are the largest class of drug targets, yet identifying and developing selective GPCR-targeting drugs is challenging. Peptides and antibodies are emerging as an superior modalities to achieve selective GPCR modulation compared to small molecules. Class A GPCRs comprise the largest number of drug targets, but present several challenges for novel biologics discovery, including: low expression levels; protein instability; limited extracellular accessible epitopes and the need to present the entire receptor as an intact antigen (i.e. not just a soluble ectodomain). Existing methods to stabilise GPCR antigens are not generically applicable to improving GPCR expression, and often result in non-functional mutant GPCRs, leading to ineffective biologics discovery. We have developed a novel and superior method called Lentiviral-Assisted Selection Enabling Receptor Engineering and Drug Discovery (LASEREDD®). LASEREDD® accelerates the preparation of GPCR samples for biologics discovery by rapidly engineering high-expressing GPCR variants from diverse, minimally mutated gene libraries. The LASEREDD® approach uses directed evolution in human cells and detailed structural and pharmacological evaluation to ensure our engineered GPCRs maintain their natural structure and function. LASEREDD®-engineered GPCR variants allow the preparation of: cell lines; virus-like particles; liposomes; and homogeneously purified protein samples with high GPCR protein content/activity, enabling biophysical and structural studies of challenging GPCRs and facilitating biologics discovery. The application of LASEREDD® to several challenging GPCR targets will be presented, along with the use of LASEREDD®-optimised GPCRs for nanobody discovery campaigns. Overall, the LASEREDD® approach promises to overcome the significant barriers that have hindered biologics discovery and optimisation at GPCR targets, paving the way for more efficient & effective discovery of GPCR biologics.