Nb.CDR3.rAAV9-sIL-1Ra

Nb.CDR3.rAAV9-sIL-1Ra is an experimental gene therapy designed for the treatment of rheumatoid arthritis (RA). Developed by researchers at the University of Massachusetts Chan Medical School, it utilizes a recombinant adeno-associated virus serotype 9 (rAAV9) vector engineered for enhanced tissue specificity. The vector's capsid is modified by grafting the complementarity determining region 3 (CDR3) of an anti-fibroblast activation protein alpha (FAPα) nanobody, allowing it to specifically target FAPα-expressing synovial fibroblasts in inflamed joints while reducing off-target transduction in the liver and muscle. The therapeutic payload is a gene encoding soluble interleukin-1 receptor antagonist (sIL-1Ra), which is expressed under the control of an inflammation-inducible promoter. By delivering sIL-1Ra directly to the site of inflammation, the therapy aims to suppress the pro-inflammatory signaling of IL-1, thereby reducing joint swelling, cartilage damage, and bone erosion associated with RA.