Overview
RAMP-UP aims to develop versatile bacterial and mammalian cell-based platforms to:
- Design efficient and manufacturable biologics
- Develop scalable bioprocesses and analytical technologies
- Rapidly mass-produce formulated biologics, including sterile fill-finish, within 100 days
Our research is focused on pandemic preparedness, particularly for SARS-CoV-2 and Avian Influenza (H5N1). The program is structured around five integrated Work Packages (WPs) that leverage the 2 cell platforms.
How to join
M.Sc. and Ph.D. students interested in become part of the RAMP-UP initiative must contact a member of the research team, who will send them a registration form. Please note that your research team will need to be compatible with the RAMP-UP Work Packages described below.
Working Packages
| WP 1 | WP 2 | WP 3 | WP 4 | WP 5 | |
| Xavier Banquy | X | ||||
| Grégory De Crescenzo* | X | X | |||
| Alain Garnier | X | X | |||
| Bruno Gaillet | X | X | X | ||
| Sophie Gobeil* | X | ||||
| Olivier Henry | X | X | |||
| Younès Messaddeq | X | ||||
| Marie-Ève Paquet | X | X | X |
*Co-director
WP1. Molecular Engineering of biologics
This strand focuses on the design, engineering, and characterization of relevant protein-based vaccines, therapeutics, and diagnostic reagents to improve their efficiency and manufacturability.
Protein antigens : Our team has developed a fast and scalable CHO cell-based platform to produce SARS-CoV-2 spike proteins, including most variants of concern, at high yields. This technology also enables the production of spike proteins from other potentially pandemic coronaviruses (e.g., SARS1, MERS, seasonal strains), with enhanced expression through protein engineering. This platform lays the foundation for rapid vaccine development in response to future coronavirus outbreaks and can be adapted to other WHO-priority viruses such as Ebola, avian influenza, Nipah, and Lassa.
Virus-like particles (VLPs) : Virus-like particles (VLPs) are promising vaccine platforms due to their ability to elicit strong humoral and cellular immune responses. Building on recent clinical advances (e.g., Medicago’s Covifenz and VBI Vaccines’ Phase I trials), our team has developed a novel CHO-based system for high-yield production of trimeric S-decorated VLPs that closely mimic SARS-CoV-2. These VLPs demonstrate potent immunogenicity at nanogram doses and can be affinity-purified in a single step. Ongoing research focuses on optimizing structural and biochemical parameters to enhance stability and immunogenicity, supported by collaborations with Ivano Biosciences and VVector Bio.
Monoclonal antibodies mAbs) and nanobodies (VHHs) : Monoclonal antibodies (mAbs) are key complementary tools in pandemic response, offering rapid protection and serving both diagnostic and therapeutic roles. To overcome challenges posed by viral mutations (e.g., SARS-CoV-2 and H5N1), our team is developing mAbs targeting conserved viral domains and designing antibody cocktails to enhance efficacy. In collaboration with NRC and Immune Biosolutions, we are leveraging AI-driven discovery platforms and exploring Fc modifications to mitigate antibody-dependent enhancement (ADE). Notably, our stable, aerosolizable llama-derived single-domain antibodies (VHHs) have shown strong protection in preclinical models and are being engineered for extended half-life. One candidate, Rimteravimab (VHH72 derivative), is currently in clinical trials.
Advanced structural and biophysical biologics characterization: Our team has developed a robust platform for the rapid purification and structural analysis of SARS-CoV-2 and other coronavirus spike (S) proteins. This enables detailed biophysical and mechanistic studies of viral entry, antibody interactions, and proteolytic susceptibility. Using advanced techniques such as ELISA, SPR, X-ray crystallography, and cryo-EM, we aim to elucidate how evolutionary changes in viral glycoproteins affect function and antibody recognition—insights that will inform the engineering of potent and manufacturable biologics.
WP2. Cell line, strain and vectors engineering
Mammalian Platform: This strand of the research aims to accelerate the production of biologics—such as recombinant proteins, monoclonal antibodies (mAbs), and virus-like particles (VLPs)—using CHO and HEK293 cells. By improving transient gene expression and pool-based systems, the team seeks faster, cost-effective alternatives to traditional clonal methods. Genomic and metabolic analyses, including CRISPR/Cas modifications, will help optimize cell performance. Various transfection techniques and custom-designed promoters will also be explored to enhance protein yield and stability.
Bacterial Platforms: This strand focuses on optimizing large-scale production of plasmid DNA and proteins using E. coli and B. subtilis, two well-established microbial platforms. By refining strain selection, DNA design, and fermentation methods, the team aims to boost yields and efficiency. Advanced genetic engineering, including CRISPR-Cas9 and autolytic systems, will be used to streamline purification and reduce reliance on antibiotics. Quality control and collaborations with industry partners will support the development of robust, scalable manufacturing solutions.
WP3. Upstream Process Intensification
Production via stable cell pools: Building on lessons from the COVID-19 pandemic, this strand aims to improve non-clonal CHO cell pool platforms for faster production of protein antigens and antibodies. By developing high cell density processes and hybrid culture strategies, the team seeks to boost yield and maintain product quality. Advanced metabolic profiling, machine learning models, and collaborations with industry partners will support real-time process control and intensification, pushing CHO-based biomanufacturing to new levels of efficiency.
Production via transient gene expression : Transient gene expression (TGE) is a key technology for producing biologics quickly, especially in urgent contexts like pandemics. While polyethylenimine (PEI) is commonly used for gene delivery, its toxicity and scalability issues limit its effectiveness. In collaboration with Feldan Therapeutics and Alterna, this strand will develop new peptide-based transfection methods and serum-free media optimized for large-scale TGE in CHO and HEK293 cells. Using model biologics, the team will refine transfection strategies and feeding regimes to improve yield and compatibility with GMP manufacturing.
Production via fermentation : To meet growing demands for biologics, especially during pandemics, this research strand explores continuous and repetitive fed-batch (RFB) strategies to intensify plasmid DNA (pDNA) production in E. coli and B. subtilis. These approaches aim to reduce downtime and increase yields in smaller facilities. Through metabolic, transcriptomic, and proteomic analyses, the team will identify key factors affecting productivity and develop optimized feeding strategies. Collaborations with NRC, Glycovax, and Biovectra will support the development of scalable, cost-efficient biomanufacturing processes.
WP4. Downstream Processing and Formulation
Efficient downstream processing (DSP) is essential for cost-effective biologics production. Current methods for purifying spike proteins, virus-like particles (VLPs), and plasmid DNA (pDNA) face scalability and separation challenges. This strand will apply a systematic, data-driven approach—combining high-throughput screening, design of experiments (DOE), and AI-based analysis—to identify optimal purification strategies. The team will also explore integrated capture technologies and develop stable formulations using preformulated media libraries, accelerating the path to clinical-grade biologics in collaboration with NRC and industry partners.
WP5. Process Analytical Technologies to streamline process development and digitalization
We are developing cutting-edge tools to enhance process control and digitalization:
SPR-based online sensing: To improve biologics quality control, this strand will develop a real-time biosensor assay using surface plasmon resonance (SPR) technology. The method will enable rapid quantification and glycosylation profiling of monoclonal antibodies, which are key to their therapeutic performance. In collaboration with HyperMabs, the team will optimize binder selection, assay conditions, and data analysis tools. The approach will also be adapted for avian influenza antigens and other biologics, with a focus on analyzing raw bioreactor samples. Strategies to reduce non-specific binding and improve sensor performance will be explored to ensure reliable, scalable analytics.
Photonic platform and Raman spectroscopy: To support better decision-making in bioprocessing, this strand will develop a photonic platform for real-time monitoring of cell cultures using advanced optical spectroscopy and fibre-optic probes. By combining multi-wavelength fluorescence data, off-gas analysis, and Raman spectroscopy—including cutting-edge techniques like FERS and CERS—the team aims to track key variables such as nutrient levels, cell viability, and product yield. In collaboration with INO, new fibre designs will be created to enhance signal detection and reduce noise, enabling precise, non-invasive monitoring directly from bioreactors.