Gene drugs are likely to be a next-generation biopharmaceutics to achieve precision therapy of various diseases such as hepatitis B and tumors. Undoubtedly, RNA interference (RNAi) is a most propounding gene therapy strategy. siRNA is a short double-stranded RNA (dsRNA) taking effects in the cytosol, rendering a better drugability than pla**id DNA. Compared to antibodies, siRNA treats diseases at a genetic level and hence works more effectively. The research and development of siRNA drugs has attracted global scientific as well as industrial interests. Nearly 60 clinical trials are at phase I-III stages for treating different diseases. The clinical and preclinical results demonstrate that siRNA is prone to degradation in vivo, difficult to be taken up by target cells, and incapable of escape from endosomes. The development of safe and efficient siRNA delivery systems are the key to clinical applications of siRNA. We are going to design and develop a series of advanced nucleic acid formulations to efficiently and specifically deliver siRNA to target cells (e.g. liver cells, leukemia cells and T cells), laying a foundation for precision gene therapy of hepatitis B and tumors. We have invented chimaeric polymersomes which can efficiently load and deliver RNA drug to target cells, effectively treating lung tumors, glioblastoma and Ulcerative Colitis. We are developing liver-targeted polymersomes for effective treatment of liver-related diseases such as hepatitis B and nonalcoholic fatty liver disease (NAFLD).
1) M. Qiu, J. Ouyang, Y.H. Wei, J. Zhang, Q. Lan, C. Deng*, and Z.Y. Zhong*, Selective cell penetrating peptide-functionalized envelope-type chimaeric lipopepsomes boost systemic RNAi therapy for lung tumor, Adv. Healthcare Mater. 2019, 1900500.
2) X. Xu, W.J. Yang, Y.N. Shi, W.X. Zhang, X. Wang, F.H. Meng, and Z.Y. Zhong*, and L.C. Yin*, Efficient and Targeted Drug/siRNA Co-Delivery Mediated by Reversibly Crosslinked Polymersomes toward Anti-Inflammatory Treatment of Ulcerative Colitis (UC), Nano Res. 2019, 12, 659-667.
3) Y.N. Shi, Y. Jiang, J.S. Cao, W.J. Yang, J. Zhang*, F.H. Meng, and Z.Y. Zhong*, Boosting RNAi therapy for orthotopic glioblastoma with nontoxic brain-targeting chimaeric polymersomes, J. Control. Release 2018, 292, 163-171.
4) Y. Zou, M. Zheng, W.J. Yang, F.H. Meng*, K. Miyata, H.J. Kim, K. Kataoka*, and Z.Y. Zhong*, Virus-Mimicking Chimaeric Polymersome Boosts Targeted Cancer siRNA Therapy in Vivo, Adv. Mater. 2017, 29, 1703285