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-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