Expression of Therapeutic Proteins in Eukaryotic Algae

Antibody-based therapeutics have proven to be very effective at treating a number of human diseases, and continue to be one of the fastest growing sectors of drug development. Such therapeutics have great potential fore the treatment of a number of cancers, and offer one of the few options available for treatment of acute infections.

Using the unicellular eukaryotic alga Chlamydomonas reinhardtii, we have developed a system for expression of recombinant proteins. Algae are an ideal system for the production of therapeutic proteins as transgenic algae can be generated in a short time, and the cost of proteins produced in algae is a fraction of the cost of proteins produced by using traditional mammalian cell cultures. Currently, monoclonal antibodies are produced by culturing mammalian cells, and capital costs for production facilities can run into the hundreds of millions of dollars. Because of these high capital and media costs, monoclonal antibodies are some of the most expensive drugs on the market.

To develop an efficient algal-based expression system, we have constructed strains of C. reinhardtii that express a number of variants of human monoclonal antibodies. We have produced several forms of an antibody to herpes simplex virus and have shown that these antibodies assemble in the algae to form fully functional molecules that bind herpes simplex proteins (Mayfield et al, 2003). We have produced antibodies specific for the CD19 protein of lymphoma tumors, and we are exploring the ability of these antibodies to bind and neutralize CD19-positive tumor cells. Recently, we generated a series of transgenic algae that express antibodies to the microorganism that causes anthrax, and have shown that chloroplast expressed anti-anthrax toxin antibodies are capable of biding the toxin at similar levels as mammalian expressed antibodies. We hope to test these molecules for their ability to neutralize anthrax toxin in animal models in the near future.

We have also produced a number of other types of therapeutic proteins, including serum amyloids and human growth hormones. Treatment with serum amyloids may be an effective treatment for the reduction of bacterial and viral infections of the gut, and production of a these proteins in algae makes oral delivery of the therapeutic proteins possible, as green algae are safe to eat. Recently, we achieved expression of therapeutic proteins that accounted for over 5% of total soluble protein produced, levels that make production of proteins in algae economically practical for any type of therapeutic protein (Manuell et al, 2006). Our challenge now is to produce and purify sufficient quantities of therapeutic proteins to begin animal-based testing.