Optimization of recombinant antiviral antibody production in the diatom Phaeodactylum tricornutum
Completed projectProject start: May 2019 | Project end: May 2022
Principal Investigator: Dr Felix Ciceron
Other participants from PML: Dr Tracey Beacham, Paul Rooks, Professor Mike Allen
Microalgae represent a promising resource for the production of various high-value products, such as lipids, polysaccharides and recombinant proteins. Among the range of microalgae model organisms, the diatom Phaeodactylum tricornutum appears to be very suitable for the production of complex recombinant proteins: some of its post translational modification features are relatively close to mammalian cells, it requires inexpensive conditions to grow (sea water and light) and advanced molecular tools have recently been developed for studying this species.
Furthermore, it has been recently shown that P. tricornutum is able to produce and secrete recombinant human monoclonal antibodies against two different viruses: Hepatitis B and the Marburg virus. Those anti-Hepatitis B and anti-Marburg virus mAbs were properly folded, secreted in the supernatant and functional in vitro.
Thus, P. tricornutum can now be considered as an interesting new platform for antibody production, especially for producing antibodies that target fast-emerging viruses, when affordable antibody-based therapies have to be rapidly set up.
The main drawback of using P. tricornutum for the production of monoclonal antibodies at industrial scale is currently the overall yield of recovered product, which is currently too low to consider this species as an economically relevant platform. This limitation may however be overcome by the rapid development of microalgae synthetic biology. Whereas conventional drawbacks with mammalian cells - such as risks of viral contaminations and medium-high costs - will hardly be solved, advances in diatoms genetics should rapidly upgrade these new hosts to a competitive level.
This project consists of enhancing the yield and practicability of recombinant protein production in P. tricornutum. It relies on the optimisation of genetic vectors combined with the establishment of a pilot scale process for the cell culture and the purification of recombinant proteins.
By combining genetic and process optimisation approaches, we aim to move from the current “proof of concept” stage, to a more streamlined process that would facilitate the progression from the cloning of foreign genes to a pilot scale culture in less than three months.