MAMMALIAN CELL FACTORIES
We are very excited to explore new production ways of biologics using mammalian cells. Therefore, we are venturing into engineering mammalian cells using novel CRISPR Cas9 technologies to boost production while increasing cells’ performance and suitability to the bioprocess demands. We are also developing novel automated bioreactors to improve the growth of mammalian cells using continuous production methods

OVERVIEW
UCL Biochemical Engineering is leading in bioprocess research by creating innovative engineering solutions for improvement in biomanufacturing, one of which is in the field of healthcare, either for the development of biologics and vaccines or cell and gene therapies. LeoRios Lab at UCL Biochemical Engineering is dedicated to taking part in the utilisation of mammalian cells to serve their purposes.

IMPORTANCE
Despite the superiority offered by bacterial and yeast cells in comparison with mammalian cells in terms of easier and more economical handling, mammalian cells are still dominating as the host to produce biologics, since it is still irreplaceable for the production of complex recombinant protein with post-translational modifications (PTMs) such as glycosylation. The significance of viral vectors in the development of viral-based vaccines also calls for the use of mammalian cells for desired virus replication. For cancer and diseases involving genetic defect, gene therapy presents huge potential. Recently, artificial chromosomes have been shot as one promising strategy for the development of such therapies.
Our group is exploring the utilization of mammalian cell cultures for a number of targets. We are currently working in de novo construction of artificial chromosomes (ACs) in mammalian cells. Optimisation is focused to achieve an efficient way to construct ACs in various mammalian cells using the help of yeast cells for large DNA delivery. We are also excited to conduct research comprising the engineering of mammalian cells using novel CRISPR-Cas technologies to boost the production while increasing cells’ performance and suitability to the bioprocess demands along with the development of novel automated bioreactors to improve cells growth serving various purposes, such as expression of gene(s), virus production, and gene therapy.

TECHNIQUES AND TOOLS
To achieve the objectives of bringing innovative engineering approaches in mammalian cells, several techniques are applied as follows.
 Bioinformatics for DNA and proteins
 CRISPR/Cas systems
 Various cloning techniques for DNA isolation and construction, recombinase-based methods
 Lipofection
 Spheroplast fusion
 Cell analysis and sorting
 Automatization techniques

POTENTIAL APPLICATION
The techniques and tools are employed to address various areas of study, including, but not limited to
 Optimization of processes, such as fermentation and DNA transfer to cells
 Modification of cell genetics for character improvements
 Complex recombinant protein production harbouring PTMs
 Viral vector-based vaccine production
 Gene therapy