The School of Chinese Medicine (SCM) and the Institute for Advancing Translational Medicine in Bone & Joint Diseases (TMBJ) have recently accomplished a significant achievement in targeted therapy for osteoporosis in collaboration with the Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences; and the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine. The researchers developed a novel aptamer-functionalised delivery system that achieves osteoblast-specific delivery of osteogenic siRNAs to promote bone formation. This new system will drive forward and accelerate the development of targeted therapies for osteoporosis. The result of the research was recently published in premier scientific journal Nature Medicine(http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3791.html).
The project was supported by grants from the Ministry of Science and Technology of China, the Natural Science Foundation Council of China, the China Academy of Chinese Medical Sciences, the Research Grants Council of Hong Kong and many other research grants. This interdisciplinary research project conducted by scientists from Hong Kong and Beijing leveraged their respective strengths. The team of Professor Lu Aiping, Dean of SCM, and Director of TMBJ, and Dr Zhang Ge, Deputy Director of TMBJ, selected the targeting ligands, prepared the delivery system and conducted bone bio-imaging analysis. Meanwhile, the team from the Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, led by Professor Lu, carried out all the animal studies. The team of Dr Zhang Lingqiang from State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, provided molecular biology support for all the in vitro studies while Kunshan Industrial Technology Research Institute supplied most of the nucleic acid reagents.
After four years of concerted efforts, researchers developed a direct osteoblast-specific aptamer and an aptamer-functionalised delivery system to restore bone mass in osteoporosis animal models.
Professor Lu Aiping said: “Not only can aptamers be used in cell-specific delivery of siRNAs, but they can also play a significant role in new drug discovery. China is rich in Chinese herbal medicine and natural products, providing a good supply of potential drugs. The studies have revealed the strong potential of developing these resources into effective new drugs to treat tumors, inflammation and infectious diseases as well as osteoporosis. Until this latest modification made on aptamer technology, clinical application of these products was hindered by their poor solubility and high toxicity. Aptamer-modified herbs and natural products show significantly improved solubility. Furthermore, cell-selectivity of aptamers enhances the therapeutic effect of herbs and natural products and also reduces their side effects for non-target cells and organs.” Recently, Professor Lu established a university-enterprise collaborative innovation platform and launched a series of projects for the development of innovative class I drugs (aptamer-drug conjugates) with different enterprises in the Mainland.
Dr Zhang Lingqiang from State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, said: “The continuous development of China’s manned space programme brings with it challenges to the physical fitness of astronauts. Microgravity-induced bone loss is one of the most serious conditions caused by the extreme environment of space. This novel delivery system could be used to prevent bone loss in astronauts and may have significant implications for the development of manned space technology.”
The project was developed from another research of Dr Zhang Ge which was published in Nature Medicine in 2012. Under the then study, an oligopeptide-based delivery system was developed to promote bone formation and facilitate the selective-enrichment of osteogenic siRNAs in osteoblasts on bone formation surfaces. However, the complicated human body requires a more accurate and safe delivery system, namely the direct osteoblast-specific delivery system.
Dr Zhang Ge described the previously developed oligopeptide-based delivery system as the first-generation system. He said: “This novel aptamer-based delivery system is an enhanced version of the first-generation system and it is a real osteoblast-specific delivery system at the cellular level.”
Professor Lu Aiping (left) and Dr Zhang Ge (second from right) lead HKBU research team to develop a novel osteoblast-specific delivery system