Cell-free protein synthesis unlocks high-throughput biologics discovery and machine learning–driven protein engineering. By decoupling cell growth from protein production, it enables rapid expression in just 5–8 hours using preprepared, stable extracts. Unlike cell-based systems, it offers precise control over reaction conditions, efficient incorporation of non-natural amino acids, and production of complex molecules from diverse scaffolds—all with a single extract. This flexibility accelerates design–build–test cycles and supports parallel screening at scale. This cutting-edge platform is fully scalable from benchtop to commercial manufacturing, offering a transformative alternative to traditional expression systems.

Next-generation insect cell lines are emerging as versatile platforms for recombinant protein and vaccine production. This presentation highlights how integrative functional genomics—including single-cell transcriptomics, ATAC-seq, and regulatory network modeling—can decode cellular heterogeneity, identify productivity-associated pathways, and guide rational engineering of expression systems. By linking omics-derived insights with cell line development, we outline strategies to improve stability, scalability, and performance, positioning insect platforms as competitive and customizable solutions for next-generation biomanufacturing.

Growth factors and cytokines are commonly used media reagents in cell culture, therapies, and research with a market valued at $740M. Many of these proteins are manufactured in E. coli as inclusion bodies which require solubilization and refolding. Opera Bioscience has developed the type 3 secretion system (T3SS) in a novel bacterial expression platform for single-step secretion of soluble heterologous proteins, achieving up to 90% purity before purification. Opera’s technology enables efficient and scalable fermentation to manufacture proteins for reagents, enzymes, and therapeutics. We will present Opera’s progress on the secretion and production of growth factors and cytokines.

We are developing an ultra-stable insulin analog using advanced protein engineering and formulation technologies from UT Southwestern. Our approach addresses fundamental biophysical instabilities such as fibrillation, aggregation, and stress sensitivity, that limit current insulin products. Importantly, elimination of fibril formation enables substantially greater flexibility in formulation design and pharmacokinetic optimization.

In the Process R&D Enabling Technologies group at Merck, we have recently established the Novel Expression Systems team to identify the most suitable hosts for the engineering and expression and of various biomolecules. We are exploring Bacillus subtilis and Komagataella phaffii (previously known as Pichia pastoris) as promising hosts that capitalize on the advantages of protein secretion.