This invention discloses a neutralizing nanobody targeting soluble
interleukin-17
receptor D (sIL-17RD), its preparation method, and its applications. The
heavy chain variable region (VHH) of this nanobody contains a
heavy chain complementarity-determining region 3 (CDR-H3) that specifically binds to sIL-17RD, with a length of 10 amino acids and containing 2–6
lysine residues. This invention provides four nanobodies: CQ5, CQ13, CQ11, and CQ6, corresponding to well-defined CDR-H1, CDR-H2, and CDR-H3 sequence combinations. This nanobody can specifically bind to and neutralize the
biological activity of sIL-17RD, reducing
chondrocyte death, promoting proliferation, and maintaining
extracellular matrix
homeostasis by inhibiting the P2rx7-NLRP3
inflammasome-mediated
chondrocyte pyroptosis pathway. This invention also protects the
nucleic acid encoding this nanobody, the
recombinant expression vector, the host
cell, the pharmaceutical composition, and the preparation method. The nanobodies described can be used to prepare drugs for the prevention and treatment of inflammatory
osteoarthritis and other
osteoarthritis. They can inhibit
synovitis, reverse
cartilage and
subchondral bone degeneration, and relieve pain, showing promising application prospects.