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| RIKEN Press Release | November 15, 2007 |
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Nano production techniques applied to gene-switching RNAResearchers find a means to extend the useful life of synthetic RNA that could be utilized to safely combat hereditary diseases. | |
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Scientists at RIKEN studying a cellular phenomenon that switches gene expression on and off have used nanotechnology techniques to create an improved 'dumbbell-shaped' version of synthetic RNA. In the process, the discovered that they may have overcome a vexing problem of how to extend the effectiveness of RNA used for clinical purposes. Reported in the Journal of the American Chemical Society, the research could ease the way to improved gene fixes in a range of genetically linked diseases in humans. In the ongoing study funded by RIKEN, researchers are seeking ways to effectively extend the useful life of so-called 'small interfering RNA' (siRNA), which figures in the expression of certain genetic traits. There is growing understanding of how siRNA acts to regulate genes, and a number of researchers have focused on this phenomenon as a way to study and possibly arrest hereditary diseases. However, synthetic siRNA developed for laboratory use has been found to destabilize quickly in biological fluids. So the RIKEN research team was looking for a new and hardier version of synthetic siRNA that would stand up long enough to be used for experimental and therapeutic purposes. The researchers noted that while other studies have been able to extend the effectiveness of siRNA, such modifications can cause a decrease in siRNA gene switching activity; there is also concern that unnatural RNA derivatives used to increase stability could be toxic to the human body. The RNA 'recipe' the RIKEN team used was to combine RNA with a gene from a firefly, then induce it to form dumbbell-shaped links in a circular formation. The process using specially developed nanotechnology techniques was seen to be reliable and reproducible, permitting production of quantities of the RNA dumbbells. The researchers theorized that the dumbbell shape would be more stable than previously developed synthetic siRNA strands. Tests showed that activity of the gene expression phenomenon was still present in the modified RNA structure. To assess their durability, samples were tested with diluted snake venom, selected for its effectiveness in breaking down mammalian enzymes. Other samples were mixed with human serum at temperatures in the range found at the cellular level. Although the modified RNA structure was found to break apart, degradation was less rapid than usual and judged by the researchers to be the first reported instance in which extended life of synthetic siRNA had been safely realized. Therefore, they predicted, their new method to stabilize nontoxic siRNA strands 'should be very useful' for future therapeutic applications. The findings were reported by researchers led by Yoshihiro Ito at Discovery Research Institute of RIKEN, Wako.
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| RIKEN, one of Japan's leading research institutes, conducts basic and applied experimental research in a wide range of science and technology fields including physics, chemistry, medical science, biology and engineering. Initially established as a private research foundation in Tokyo in 1917, RIKEN became an independent administrative institution in 2003. For more information, visit www.riken.jp | |
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