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PHAECTORY: Project challenge Next Previous

Nowadays, therapeutic antibodies play an important role in therapy and diagnostics of disease. This can be exemplified by therapeutic antibodies against varies cancer types. Rituximab, Trastuzumab and Bevacizumab are the three top-selling antibodies of Roche with sale figures up to 6.7 billions of CHF in 2012.

Roche antibodies
* Billions of CHF, in 2012. Source: Roche

This increasing need for antibodies led us to think about a good way for the easy and cheap antibody production. Looking at the requirements for antibodies useful in therapy and diagnostic several challenges have to be solved. First of all, antibodies have to be very pure for save applications and they need several posttranslational modifications. Additionally the folding and disulfide bridge pattern must be correct. However the currently used production systems have several limitations:

E. colia) The gram-negative bacterium Escherichia coli is widely used for protein expression, because it is fast growing and cheap in cultivation. However, the production of proteins with complex folding pathways and posttranslational modifications is difficult, because E. coli lacks the appropriate chaperones and glycosylation machineries.

Yeastb) The baker's yeast Saccharomyces cerevisiae can produce complex proteins, but its glycosylation machinery does not match the posttranslational modification pattern, which is required for human applications.

mammalian cell culturec) Mammalian cell cultures can produce complex proteins, which fulfill all requirements for human applications. However, production of complex proteins in cell cultures is expensive and they are very sensitive to contaminations, even with human pathogens.

Plantsd) Similar to cell cultures, plants are also able to produce complex proteins, which are correctly folded and posttranslationally modified. Yet the amount of protein that can be obtained is very low and the growth is quite slow.

Another important disadvantage of all the above-mentioned systems (a to d) is that the target proteins have to be extracted from the cell with high purity. This process is cost-intensive and often complicated! It would therefore be great to have a production host, which directly secretes the target protein from the cell.

We therefore aimed at establishing a system for iGEM, which can produce complex proteins and is able to secrete them into the surrounding medium. These organisms exist: Microalgae! Especially Phaeodactylum tricornutum is able to produce and secrete therapeutic antibodies in huge amounts at low costs with the correct posttranslational modifications. On top, it is carbon dioxide neutral and driven by sunlight. Because of all these advantages, we decide to establish PHAECTORY as a new chassis for the iGEM competition.