An AAV-Based NF-κB-Targeting Gene Therapy (rAAV-DMP-miR533) to Inflammatory Diseases
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-06-01
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| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/an-aav-based-nf-b-targeting-gene-therapy-raav-dmp-mir533-to-inflammato-peer-reviewed-fulltext-article-JIR |
| _version_ | 1811246671572500480 |
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| author | Luo T Wang Y Tang H Zhou F Chen Y Pei B Wang J |
| author_facet | Luo T Wang Y Tang H Zhou F Chen Y Pei B Wang J |
| author_sort | Luo T |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-04-12T14:57:39Z |
| format | Article |
| id | doaj.art-1022d157607942bdbaf283df1d648d86 |
| institution | Directory Open Access Journal |
| issn | 1178-7031 |
| language | English |
| last_indexed | 2024-04-12T14:57:39Z |
| publishDate | 2022-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj.art-1022d157607942bdbaf283df1d648d862022-12-22T03:28:11ZengDove Medical PressJournal of Inflammation Research1178-70312022-06-01Volume 153447346675935An AAV-Based NF-κB-Targeting Gene Therapy (rAAV-DMP-miR533) to Inflammatory DiseasesLuo TWang YTang HZhou FChen YPei BWang JTao 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, microRNAhttps://www.dovepress.com/an-aav-based-nf-b-targeting-gene-therapy-raav-dmp-mir533-to-inflammato-peer-reviewed-fulltext-article-JIRnf-κbinflammationtherapyaavmicrorna |
| spellingShingle | Luo T Wang Y Tang H Zhou F Chen Y Pei B Wang J An AAV-Based NF-κB-Targeting Gene Therapy (rAAV-DMP-miR533) to Inflammatory Diseases Journal of Inflammation Research nf-κb inflammation therapy aav microrna |
| title | An AAV-Based NF-κB-Targeting Gene Therapy (rAAV-DMP-miR533) to Inflammatory Diseases |
| title_full | An AAV-Based NF-κB-Targeting Gene Therapy (rAAV-DMP-miR533) to Inflammatory Diseases |
| title_fullStr | An AAV-Based NF-κB-Targeting Gene Therapy (rAAV-DMP-miR533) to Inflammatory Diseases |
| title_full_unstemmed | An AAV-Based NF-κB-Targeting Gene Therapy (rAAV-DMP-miR533) to Inflammatory Diseases |
| title_short | An AAV-Based NF-κB-Targeting Gene Therapy (rAAV-DMP-miR533) to Inflammatory Diseases |
| title_sort | aav based nf kappa b targeting gene therapy raav dmp mir533 to inflammatory diseases |
| topic | nf-κb inflammation therapy aav microrna |
| url | https://www.dovepress.com/an-aav-based-nf-b-targeting-gene-therapy-raav-dmp-mir533-to-inflammato-peer-reviewed-fulltext-article-JIR |
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