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BRIGHTON: A new method for producing large quantities of the blood protein human serum albumin, or HSA, from rice seeds has been developed.
HSA is widely used within the medical field, from treating burns to the production of vaccines. The production from human blood is limited and potentially unsafe. Molecular farming of this protein could produce a cost-effective, safer and mass-producible method of obtaining this high demand protein.
"It will generate a benefit for human healthcare and decrease the potential risks from plasma-derived HAS," said lead author Daichang Yang, from the Engineering Research Centre for Plant Biotechnology and Garplasm Utilisation at Wuhan University in China, of the paper published in Proceedings of the National Academy of Science today.
Choosing a host
HSA is extensively used for clinical applications and the market for it is growing every day. The shortage of HSA available and the safety concerns surrounding plasma-derived HSA (pHSA) - the possibility of transmission of blood-derived infectious diseases such as HIV and hepatitis, for example - have lead biotechnologists around the world to explore new ways to produce the human protein.
It is possible to create recombinant HSA (rHSA) in non-animal derived sources. This technique is referred to as medical molecular farming. Many different hosts systems have been trialled over the years, from the simple bacteria Escherichia coli to tobacco leaves, but most achieved very low levels of expression.
An rHSA expression level of 11.5% of protein was achieved in a recent study in a rice cell culture, yet here again the system proved not to be cost-effective.
Rice seeds as a host system
Yang and colleagues were able to produce large-scale amounts of rHSA at cost-effective ways using transgenic rice seeds as bioreactors: creating Oryza sativa recombinant HSA (OsrHSA). OsrHSA has been found to be comparable to pHSA in terms of its biochemical properties and functions.
Targeting the specific area of the transgenic rice seed where OsrHSA is expressed, the team focused their efforts on analysing the potential of the transgenic line. The group showed that OsrHSA was significantly similar biochemically and structurally to the human protein.
Testing the protein further, they found the binding capacity and promotion of cell growth of the rice recombinant form performed at the same level as pHSA. Finally the team tested the effects of OsrHSA versus pHSA on the treatment of liver cirrhosis in rats. Again, the results found both forms of the protein equally effective.
As safety is a major issue in medical molecular farming, the immunogenicity of the transgenic protein was assessed and here again, it was deemed similar enough to the human protein to be safe. It is also possible OsrHSA might be safer than pHSA or other expression systems at this level.
