One can’t squeeze blood from a turnip, but new research suggests that a bit of transgenic tweaking may make it possible to squeeze blood — or at least blood protein — from a grain of rice. In a study published online today in the Proceedings of the National Academy of Sciences, researchers describe rice seeds that can produce substantial quantities of a blood protein called human serum albumin, or HSA1.
HSA is in high demand around the world, both for its role in drug and vaccine production and for use in treating patients with severe burns and other serious conditions such as haemorrhagic shock and liver cirrhosis. The primary source of therapeutic HSA is donated human blood. To overcome limitations caused by blood shortages and contamination of donated blood by viruses, researchers worldwide have been working to create functional HSA either synthetically, with the help of yeast and bacteria, or in transgenic organisms such as cows and tobacco.
In China, which has suffered from HSA shortages and contaminated blood supplies, the idea of using an abundant crop like rice to supplement or even supplant the current albumin supply is an attractive one. “We could ease demand for HSA and reduce the potential risk of spreading viruses in blood plasma. That’s what prompted me to do something like this,” says Daichang Yang, a plant biotechnologist at Wuhan University, China, who led the research.
Part of the difficulty in producing synthetic or laboratory versions of HSA, however, has been developing a system with a high yield, low cost and low risk of immune reaction. Yang thinks that his seed-based method has the potential to satisfy all of those requirements. “Scientists have been using plants to produce HSA for two decades, but the yield is too low,” he says. But seeds have evolved to be specialized for protein storage, providing the optimal bioreactor for HSA production. “The higher yield could allow for lower costs,” he says.
Yang and his colleagues inserted the gene encoding HSA into their rice plants in such a way that the gene was activated during seed production, and the resulting protein was stored in the rice grain along with nutrients normally used to help nurture a germinating embryo. The final product was a crop of rice seeds in which HSA made up more than 10% of the seeds’ total soluble protein — one of the best yields of recombinant protein from plants to date.
It was relatively simple for Yang to extract HSA from the grains. Because the rice genome was completed in 2005, he was able to use this information to separate the human protein from those of rice.
The rice-derived protein was shown to be functionally equivalent to the version found in human blood plasma. Not only were the two chemically and physically identical, but they were also similar when tested for medical efficacy and immune reactivity. In rats with liver disease, both types of HSA proved equally effective in relieving symptoms associated with cirrhosis. And rats that were given rice-derived HSA showed no stronger immune reaction than animals that had been given the plasma-derived version.
“This recombinant method has a good shot at making HSA more abundantly and more safely than human plasma, and it will at least have a shot at being as cost-effective,” says William Velander, an expert in genetically engineered therapeutics at the University of Nebraska–Lincoln.
Don Brooks, who develops synthetic biocompatible materials at the University of British Columbia in Vancouver, Canada, and who has created his own synthetic version of the HSA protein, agrees. “I’m convinced that what they’ve produced is a good reproduction of the human material,” he says. “The lab work they’ve done is pretty impressive. They still have to do it in people to be sure it’s as safe as native material, but it’s looking pretty good.”
Yang aims to move into human testing next. He has submitted his first clinical-trial application to the US Food and Drug Administration, and hopes to begin testing the rice-derived HSA in humans within the next two years.
- He, Y. et al. Proc. Natl Acad. Sci. advance online publication http://dx.doi.org/10.1073/pnas.1109736108 (2011).