Establishment of Key Techniques for Developing small RNA Drugs Derived from tRNA of Traditional Chinese Medicines

Jiang Zhi Hong, Yan Tong Meng, Cao Kai Yue, Pan Yu

Macau University of Science and Technology

Small interfering RNA (siRNA) drugs hold tremendous potential in the field of precision medicine. However, the development of the small RNA drugs in China is severely constrained by the lack of targets for “orphan diseases” and the patent barriers imposed by the international pharmaceutical companies. To investigate the "dark matter" of RNAs in traditional Chinese medicines (TCM) whose pharmacological activities have long been overlooked, research team established a series of key techniques for exploring small RNA drugs derived from tRNA of TCM. In particular, the large-scale platform for the extraction of TCM RNA using the PARI method has overcome the challenge of RNA extraction from polysaccharide-rich TCM. Academically, research team is the first in the world to report the pharmacological activity of tRNA and its fragments from TCM, proposing the scientific perspective that “TCM tRNA and its fragments are pharmacologically-active components that can’t be ignored.” This expands the knowledge of active ingredients in TCM and opens new thoughts for discovering the active components and new drugs from medicinal plants. It enhances the efficiency and possibilities for discovering new drug targets, providing guidance for the development of next generation of RNA drugs. Industrially, research team discovered siRNA from Chinese yew against ovarian cancer and siRNA from Ginseng against myocardial ischemia, both of which have received patent authorization and achieved successful translation under the model of “Collaboration between Macau and Hengqin”. This achievement sets a new record for technology transfer in Macau’s universities and promotes the moderate diversification of Macau's economy in the “1+4” framework.

Fig 1 TCM tRNA and its fragments are pharmacologically-active components that can’t be ignored

Fig 2 Ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) analysis of TCM RNA

Fig 3 Patents were successfully transferred to the pharmaceutical companies in Hengqin for new drug development under the model of “Collaboration between Macau and Hengqin”