iBET’s research in Virus-based biopharmaceuticals ranges from gene to product
Gene therapy is a major area of research, focusing on the development of platforms for the production and purification of retrovirus, lentivirus, adenovirus – of human and canine origin, adeno-associated virus, Rhabdovirus and baculovirus
We work on the optimization of producer cell lines with the aim of improving not only the vector yield, but also to increase vector quality by enhancing its potency and efficiency in delivering therapeutic gene(s) to target cells.
On the upstream bioprocessing our research aims at devising strategies to monitor, control and optimize product titer and quality. On the downstream processing we develop innovative solutions for reducing manufacturing costs while increasing product recovery yields, quality and safety.
Complementary to the bioprocess cycle, we also work on the development of analytical assays to characterize cells, host-virus interactions and product quality and potency. The data generated feed new models for comprehensive readouts of process performance. In many of our projects we collaborate with iBET’s spin-off GenIbet for the production of Phase I/II clinical-grade material under cGMP.
Cell Line Development
At iBET we employ advanced tools on molecular biotechnology and synthetic biology, such as recombinase mediated cassette exchange (RMCE), CRISPR-Cas9 and other genetic engineering technologies, for the generation of modified human and insect cell lines.
To develop customized bioprocesses for each type of viral vector we assess:
- Expression systems (transient and stable expression)
- Culture systems (dynamic and static; suspension and adherent)
- Bioreactor systems (e.g. stirred-tank, wave bioreactors)
- Bioreactor types (glass; stainless-steel; single-use)
- Operation modes (batch, fed-batch, perfusion and continuous)
We develop cutting-edge GMP-compatible processes for purification of gene therapy products, contributing to the design of disposable membrane cartridges and new chromatographic matrices, in collaboration with several industrial partners (e.g. Merck Millipore, Sartorius, Pall Lifescience and GE).
Monitoring and Control
Transcriptomics, metabolomics (HPLC, 13C/1H-NMR and GC-MS) and Fluxomics (Classical Metabolic Flux Analysis, 13C-based Metabolic Flux Analysis and Metabolic Pathway Analysis) are applied to guide cell genetic manipulation and media supplementation towards improved productivities and/or desirable phenotypic traits. The in-depth characterization of producer cells and bioprocess key parameters translates in rational and target-oriented optimization strategies.
Product Characterization and Purity Assessment
We have implemented analytical techniques for detection of product and process-related impurities (e.g. chemical, host-cell derived, endotoxins, mycoplasma, etc), employing chromatographic, electrophoretic and biochemical tools. In-depth characterization of viral particles is also available (e.g. size, zeta potential, population distribution, aggregation state).