Recently, a joint research team composed of Professor Yin Dachuan's Laboratory of Biomacromolecules and Professor Qian Airong's Laboratory of Bone Metabolism, has made important progress in the field of RNA delivery vehicles. The team's research found that cationic polymer polyvinylamine (PVAm) can be used for the in vitro and in vivo delivery of various RNAs, and has the advantages of high transfection efficiency, good safety, and good economy. Journal of Controlled Release (2022, 345, 20-37).
Full text link: https://www.sciencedirect.com/science/article/pii/S0168365922001134。
The main bottleneck of current RNA drug development is that it is difficult for delivery vehicles to meet strict requirements for safety and efficacy at the same time. The classic polyethyleneimine (PEI) carrier has high transfection efficiency due to its strong binding ability with nucleic acid molecules and the existence of the intracellular "proton sponge effect", but at the same time, its cytotoxicity is also strong. The affinity between polyvinylamine (PVAm) and RNA is moderate, and it has an intracellular "proton sponge effect", which can not only effectively protect RNA from being degraded during the circulation process, but also promote the efficient intracellular release of RNA. The research results show that PVAm can deliver different sizes of RNA (siRNA, miRNA and recombinant RNA, etc.) to normal cells, tumor cells, stem cells, etc., and has better transfection effect than the current commercial Lipofectamine 2000 and INTERFERin PEI, and has cytotoxicity. lower. Using PVAm as a carrier to deliver miR-34a to xenograft human osteosarcoma mice has a significant inhibitory effect on tumor growth; delivering si-ApoB to high-fat diet-induced hyperlipidemia mice can significantly reduce blood lipid levels in mice; At the same time, the PVAm delivery system had no obvious effect on the liver and kidney function of the two model animals, and no obvious immunogenic effect.
In addition, PVAm, as a commonly used bulk chemical in industry, is much less expensive than existing commercial RNA carriers. Therefore, the research results of this project will provide a high-efficiency, low-toxicity and economical candidate carrier for the development of next-generation RNA drugs.
The first author of this paper is Assistant Professor Tian Ye, Ph.D student Zhao Yipu and postdoctoral fellow Yin Chong are the co-first authors, the corresponding authors are Associate Professor Deng Xudong, and Professor Yin Dachuan and Professor Qian Airong are the co-corresponding authors. The research work was supported by the National Natural Science Foundation of China, the Key R&D Program of Shaanxi Province, and the Fundamental Research Funds of Central Universities. The relevant research results of this project have been authorized Chinese invention patent (application of cationic polyvinylamine linear polymer as transgenic carrier, ZL201811099409.8).
