FULL RANGE SERVICE: FROM GENE TO PROTEIN

iBET’s Bioproduction Unit offers late-stage R&D, scale up and technology transfer services, from small-scale feasibility studies to large-scale production and purification, and technology transfer to GMP (provided through GenIbet, www.genibet.com). At iBET a full set of instruments and strategies have been established to develop integrated bioprocesses and analytical methods for the production, purification and characterization of virus-based biopharmaceuticals. The infrastructure is located in a BSL2 facility allowing scale-up to 50 L.

Virus-based pharmaceuticals

• Gene therapy viral vectors:
  • Lentivirus (HIV);
  • Adeno-associated virus (AAV);
  • Adenovirus (AdV5 based, CAV);
  • Retrovirus (MLV);
  • Baculovirus;
  • Rhabdovirus (Maraba virus).
• Virus-like particles (VLPs):
  • Rotavirus;
  • Porcine parvovirus;
  • MLV;
  • HIV;
  • Hepatitis C;
  • Influenza;
  • Dengue;
  • Zika.
• Vectored vaccines:
  • PPRV;
  • Rinderpest;
  • RHDV.

Upstream processing

• Cell lines:
  • Mammalian cells: HEK293, PerC6, CAP, Caco2, MRC-5, Sp2/0, BAE, Vero, MDCK, DK, CHO, A549, ExpiCHO-S™ and Expi293F™;
  • Insect cells: Sf-9, Sf-21, High Five, ExpiSf9™ and super Sf9.
• Expression systems:
  • Stable expression in mammalian and insect cells;
  • Transient expression, e.g. transfection and insect cells-baculovirus expression vector system (IC-BEVS).
• Culture systems:
  • Anchorage dependent cells, e.g. microcarrier technology in bioreactors;
  • Single cell suspension.
• Bioreactor systems/types and operation modes:
  • Stainless-steel and single-use bioreactors;
  • Environmentally controlled stirred tank (0.5 L to 50 L) and Wave bioreactors (0.5 L to 25 L);
  • Batch, Fed-batch, perfusion and continuous.

Downstream processing

• Purification of secreted and intracellular viral particles;
• Ultracentrifugation;
• Membrane technology: ÄKTA Crossflow – scalable, ultrafiltration systems;
• Chromatography: ÄKTA Platform Technology (Pure, Avant and Pilot);
• Continuous and multi-column chromatographic purification systems.

Product Characterization

• Impurities: DNA, Host Cell Protein, product related impurities (e.g. empty capsids);
• Titration protocols for infectious viral particles, e.g. flow cytometry, TCID50, plaque assay and MTT assay;
• RT-qPCR for genome-containing viral particles and for adventitious viruses;
• Capillary Electrophoresis;
• ELISA for transgene expression and for process contaminant detection;
• Nanoparticle tracking analysis (using NanoSight®) for physical viral particles quantification;
• Mass spectrometry;
• Transmission electron microscopy (negative staining and immunogold labelling);
• Dynamic light scattering;
• Surface plasmon resonance;
• Bio-layer interferometry technology;
• Tunable Resistive Pulse Sensing (qNANO);
• Analytical chromatographic methods for purity assessment;
• Cell-based potency assays.

Associated Services

At iBET, we develop mammalian and insect cell lines for stable expression of virus-based biopharmaceuticals using advanced molecular biotechnology and synthetic biology tools (e.g. recombinase mediated cassette exchange (RMCE), metabolic engineering and CRISPR-CAS9). We also develop computational biology methods (e.g. dielectric and fluorescence spectroscopy, holographic imaging) for on-line monitoring of cell concentration and viral particles production.

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