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Prof. Dr. Ralph Bock

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Dr. Ulrike Glaubitz

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Rouhollah Barahimipour, Juliane Neupert and Ralph Bock

Efficient expression of nuclear transgenes in the green alga Chlamydomonas: synthesis of an HIV antigen and development of a new selectable marker

Plant Molecular Biology, 8.01.2016, doi: 10.1007/s11103-015-0425-8

Production of an AIDS vaccine in algae

Development of a new production site for pharmaceuticals

February 09, 2016

Today, plants and microorganisms are heavily used for the production of medicinal products. The production of biopharmaceuticals in plants, also referred to as “Molecular Pharming”, represents a continuously growing field of plant biotechnology. Preferred host organisms include bacteria, yeast and crop plants, such as maize and potato – plants with high space demands and maintenance requirements. With the help of a special algal strain, the research team of Prof. Ralph Bock at the Max Planck Institute of Molecular Plant Physiology in Potsdam-Golm strives to develop a more efficient and resource-saving system for the production of medicines and vaccines. They tested its practicality by synthesizing a component of a potential AIDS vaccine.

The use of plants and microorganisms to produce pharmaceuticals is nothing new. In 1982, bacteria were genetically modified to produce human insulin, a drug that saves the lives of millions of diabetics every year. The transgenically synthesized insulin is 100% compatible with the immune system of the patients and, moreover, makes the laborious extraction of insulin from the pancreases of billions of slaughtered pigs and cows per year unnecessary.
Plants that have been used as production hosts for pharmaceuticals include, for example, tobacco, maize, rice, soybean, rapeseed and potato. However, most of these plants are primarily used as food and animal feed, and their dual use could result in potential conflicts. Moreover, these crop plants are often demanding regarding their space requirements, growing conditions and maintenance.

Chlamydomonas reinhardtii - a single-cell green alga: Test of succesful gene integration for a potential AIDS vaccine production. Zoom Image
Chlamydomonas reinhardtii - a single-cell green alga: Test of succesful gene integration for a potential AIDS vaccine production. [less]

In many respects, algae compare favorably with crop plants: they are unpretentious, display a high resource efficiency and grow fast. Moreover, they have the potential to be directly used for human consumption, thus making cost-intensive purification unnecessary and resulting in a reduction of the manufacturing costs by up to 60%. In the future, it therefore may become possible to develop vaccines that can be delivered painlessly by simple oral consumption.

Over the last three decades, the single-celled green alga Chlamydomonas reinhardtii has become increasingly popular among plant biologists. It is a freshwater alga that can be found almost everywhere in the world. Chlamydomonas is a model organism in basic research and has been extremely well characterized. Many molecular tools have been developed for research with this alga, including methods for genetic modifications. But why aren’t we using algae for biotechnological purposes already?

Algae are a rather diverse group of organisms, and the application of existing tools and methods to an alga is often far from straightforward. Also, tools that have been developed for Chlamydomonas often cannot be directly transferred to other algal species, such as algae that produce higher amounts of biomass or species that grow more efficiently in sea water. Moreover, even in Chlamydomonas, stable genetic modifications are still challenging. After the new genetic information is transferred into the genome of the alga, it is often not or not efficiently used and, what’s more, the alga can silence the foreign information over time, resulting in the loss of synthesis of the new protein. The research team of Prof. Ralph Bock seeks to generate improved algal strains to make them a competitive system in biotechnology.

In their latest study, the researchers used a gene that encodes an antigen of the HI virus. They optimized the foreign genetic information such that it allows the alga to better “understand” it and translate it more efficiently into the corresponding protein. To this end, the researchers identified characteristics of the genetic makeup of the alga and modified the foreign gene sequences accordingly. “Additionally, we generated an alga strain that is able to use the new genetic information much more efficiently than conventional strains”, explains Dr. Juliane Neupert, researcher at the Max Planck Institute. The optimized foreign gene, encoding a potential component of an AIDS vaccine, was then transferred into the new alga strain to test the efficiency and practical applicability of the new production system.

78 million people worldwide are infected with HIV, a virus that killed already more than 39 million people. Every year, 2 million people are newly infected, mainly in developing countries. This underlines the urgent need to develop an effective AIDS vaccine. More than 30 years of research resulted in the identification of a few virus proteins that are efficiently recognized by our immune system and, thus, are candidate components of a future AIDS vaccine. Among them is the so-called p24 protein.
“We were able to optimize the p24 gene structure and then transferred it into the genome of the optimized Chlamydomonas strain with the help of genetic engineering methods”, explains Rouhollah Barahimipour, first author of the study. “The alga was now able to use the optimized gene and to accumulate the p24 protein”, he confirms.

The researchers in Potsdam-Golm were able to identify the reasons for previous difficulties with synthesizing foreign proteins in Chlamydomonas. At the same time, they developed a new, highly efficient production platform for pharmaceutical proteins. Their work indicates a bright future for algae in biotechnology. As soon as a new vaccine is identified, this system can now be used for fast and efficient large-scale production. The research team published their results in the journal “Plant Molecular Biology”.

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