| Summary: | Tao Luo,1 Yile Wang,1 Hailin Tang,1 Fei Zhou,2 Ying Chen,3 Bing Pei,4 Jinke Wang1 1State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, People’s Republic of China; 2School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, 521041, People’s Republic of China; 3School of Medical Technology, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 4Department of Clinical Laboratory, the Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, Jiangsu, 223800, People’s Republic of ChinaCorrespondence: Jinke Wang, State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, People’s Republic of China, Email wangjinke@seu.edu.cnBackground: The inflammatory diseases pose a great threat to human health. Variant anti-inflammatory agents have been therefore developed. However, the current anti-inflammatory drugs are still challenged by low response and side effects. There remain great unmet treatments to inflammatory diseases.Methods: In this work, we fabricate a recombinant adeno-associated virus (rAAV), rAAV-DMP-miR533, by packaging a DNA molecule DMP-miR533 into AAV, in which DMP is a NF-κB-activatable promoter composed of a NF-κB decoy and a minimal promoter and miR533 codes an artificial microRNA targeting NF-κB RELA. We evaluate the in vitro and in vivo anti-inflammatory effect of the virus with inflammatory cells and the mice of three typical inflammatory diseases including the dextran sulphate sodium-induced acute colitis, imiquimod-induced psoriasis, and collagen-induced arthritis.Results: We found that rAAV-DMP-miR533 had marked anti-inflammatory effect in both cells and mice. In addition, rAAV-DMP-miR533 showed biosafety in mice.Conclusion: This study thus provides a promising gene therapy to variant inflammatory diseases by directly targeting NF-κB, an established hub regulator of inflammation.Keywords: NF-κB, inflammation, therapy, AAV, microRNA
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