An AAV-Based NF-ΚB-Targeting Gene Therapy (rAAV-DMP-miR533) to Inflammatory Diseases

Background: 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-??B-activatable promoter composed of a NF-??B decoy and a minimal promoter and miR533 codes an artificial microRNA targeting NF-??B 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 sodiuminduced 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-DMPmiR533 showed biosafety in mice. Conclusion: This study thus provides a promising gene therapy to variant inflammatory diseases by directly targeting NF-??B, an established hub regulator of inflammation.

Automated summary

The study presents a recombinant adeno-associated virus (rAAV-DMP-miR533) that shows significant anti-inflammatory effect by directly targeting NF-κB. It also demonstrates the biosafety of the virus in mice.