News_Global Crisis_Aids

A rice harvest dripping with bloody potential

An old dream of biotechnologists is to produce human proteins not by microbes or animals, but in an 'unbloody' way: by genetically manipulated or transgenic plants. Such plants can be grown and harvested, and the blood proteins extracted are 100 per cent safe. No virus contamination can harm us. It also eliminates the risk of spreading diseases. What about growing rice which is manipulated to produce blood proteins? Scientists from Wuhan University have made such a breakthrough. A report was published on October 31 in Proceedings of the National Academy of Sciences. The highly sought-after plasma protein called human serum albumin (HSA) can now be produced at high yield and purity in rice instead of isolating HSA from blood. HSA is used for the treatment of blood loss, serious burns, and abdominal fluid retention caused by cirrhosis (scarring) of the liver. In addition, HSA has served as a vehicle for vaccine and drug delivery, and as a cell culture supplement in the production of vaccines and pharmaceuticals. Now the mainland authors have demonstrated large-scale purification and functional equivalence to human HSA. They have potentially developed a very good alternative to provide HSA in the clinic. Moreover, world rice production is expected to touch a record 480.5 million tonnes this year. There is a higher output in Asia, Egypt (despite revolution), Argentina, Mozambique, the United States and Russia, according to the United Nations Food and Agriculture Organisation. There is high demand for plasma HSA, but it is in really short supply. At present, the only supply of HSA is that extracted from human blood. Besides the limited availability of blood donors, using plasma HSA also has a high risk for spreading diseases, such as Aids and hepatitis. Investigator Professor Yang Daichang of Wuhan University considers using plant-based production to satisfy market demand and reduce the risk. Yang and his colleagues are not the first to attempt genetically engineering human HSA production in other species. Yeast, bacteria, potatoes, and tobacco plants have all been tried, but each has met with feasibility issues. The problem with microbial HSA has been the tiny traces of microbial contaminants. They are either toxic or induce immune reactions in humans, which means they require extensive purification and this adds tremendously to the costs. HSA produced in potatoes or tobacco does not carry such contamination risks, but neither of these sources has provided sufficient yield to be cost-effective.

To bump up yield, Yang and his colleagues turned to rice. They targeted the part of rice we eat, the endosperm inside the seed, a natural nutrient storage organ. This is an excellent site for the accumulation and long-term stable storage of recombinant proteins. By driving expression of the HSA gene in the endosperm, the team managed to obtain 2.74 grams of pure HSA protein per kilogram of rice seed, more than 25 times the 0.1 grams of HSA collected from 1kg of tobacco leaves. In addition to obtaining a high yield, the rice-derived HSA shared the same molecular weight, crystal structure, molecular binding sites, and other biochemical characteristics as that of blood-derived HSA. These similarities translated to functional equivalence in tests for ligand binding, promotion of cell growth in culture, and the treatment of fluid retention in a rat model with liver cirrhosis. The rice-derived HSA also displayed an equivalent immunogenicity to that of plasma HSA. That is, animals injected with either rice HSA or plasma HSA developed similar immune reactions. However, before rice HSA can be used in humans it will need to go through extensive clinical trials. Furthermore, to generate sufficient quantities of HSA to meet global demand - an estimated 500 tonnes a year - production will need to be scaled up to open-field farming. So, high-value human proteins will in future grow on muddy rice paddies. Reinhard Renneberg has been professor of bioanalytical chemistry at Hong Kong University of Science and Technology since 1994