CHO cells exhibit specific cellular productivities far below theoretical maximums, primarily due to suboptimal allocation of biosynthetic capacity. We have developed (i) an automated analytical technology that can identify the exact critical cellular parameters restricting productivity, and (ii) highly-specific chemical additives that can optimally titrate those parameters to ‘rewire’ the cell and release previously untapped biosynthetic capacity. This rapid ‘diagnose-and-fix’ process can achieve significant improvements in product titre and quality.

Recombinant protein expressing cell lines are essential tools in drug discovery. However, achieving bespoke, physiologically relevant expression levels remains a significant challenge. This talk describes approaches to control protein expression levels in mammalian cell systems, drawing on work from an internal PhD project and the cell line generation team at GSK. Methods covering different points of regulation will be discussed, as well as applications to membrane proteins and complex targets.

Current mammalian cell engineering often targets known pathways, yet key production traits are polygenic and context dependent, limiting generalisability. CRISPR/Cas9-based pooled screens enable systematic discovery of novel regulators, though lentiviral delivery presents biosafety and integration challenges. Recombinase-Mediated Cassette Exchange offers a precise, non-viral alternative via single-copy insertion at defined loci, improving screening robustness. This presentation highlights RMCE-based genome-wide CRISPR screening strategies and key design considerations to enhance therapeutic protein production in CHO cells and HEK293 cells.

To address the scalability and cost challenges of rAAV manufacturing, we developed an engineered HeLa-S3 platform. By performing systematic gain- and loss-of-function screens, we generated a comprehensive gene-level map of host determinants for rAAV biogenesis, identifying multiple regulatory pathways that serve as targets for host engineering. As a proof of principle for this screening approach, CEBPA/B was identified as a central regulatory node. The resulting CEBPA-overexpressing host, combined with process intensification, enabled a 10-fold increase in volumetric rAAV productivity. This strategy of combining CRISPR-guided host engineering with perfusion bioreaction establishes a scalable, high-performance alternative to traditional transient transfection for rAAV production.

Comprehensive understanding of TCR-antigen engagement is essential for advancing T cell immunotherapies, but traditional TCR refolding from inclusion bodies is labor-intensive and can be inefficient. We have developed a robust platform for producing soluble TCRs in CHO cells. A straightforward mutational strategy enabled high-yield of the deglycosylated TCR (dgTCR) and rapid structural characterisation of TCR-pMHC complexes. Notably, just 20 ml of cell culture provided sufficient material to screen over 350 crystallisation conditions, resulting in high-resolution datasets. This efficient methodology provides a scalable alternative to traditional production routes, accelerating the structural study and development of TCR-based therapeutics for cancer and beyond.

The Baculovirus-based BacMam system has recently regained attention through major therapeutic advancements. The production of complex bio-nanoparticles demands large transgenes and tunable expression, reviving this powerful platform. This presentation will highlight transient applications, recent progress, and introduce our newly developed REM-BAC system for rapid, efficient, and manifold baculovirus-mediated generation of stable mammalian cell lines via viral-footprint-free and site-specific genome integration.

Arboviruses of the genus Orthoflavivirus remain a persistent and re-emerging global health threat. Virus-like particles (VLPs) are safe, efficient tools that mimic native antigenicity, providing a versatile platform for developing reliable diagnostics, assays, vaccines, and immunotherapies. We established a streamlined pipeline for the production, purification, and characterisation of authentic Orthoflavi-VLPs serving as mimetic surrogates for live viruses in suitable applications, leveraging their unique advantages.

Virus-like-particles (VLPs) can be produced by co-expression of viral structural proteins and offer various options of modifications for specific applications. This talk will be about the plasmid-based production of diverse VLP formats in insect cells the following purification strategies as well as the in-depth analysis of the obtained complex VLPs including special nano-cytometry. Finally examples of applications will be given ranging from basic research to drug development and vaccination approaches.