Gao JL, Li Z, Calderon-Perez R, Pavek A, Kim L, McDermott DH, Murphy PM (2026) Gene therapy via CRISPR/Cas9-mediated Cxcr4 disease allele inactivation reverses leukopenia in WHIM mice. J Clin Invest 136(5):e202073. doi: 10.1172/JCI202073 PMID: 41505207
Objective: To provide proof of principle that CRISPR/Cas9-mediated inactivation of the Cxcr4 disease allele, combined with nongenotoxic HSC- targeted conditioning, may offer a safe and effective gene therapy strategy generalizable to all WHIM-causing mutations.
Summary: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is an immunodeficiency caused by autosomal dominant hyperfunctional mutations in chemokine receptor CXCR4 that promote panleukopenia due to BM retention. The authors modified their previous protocol by adding conditioning with a nongenotoxic CD117-targeted immunotoxin, CD117-antibody-saporin-conjugate.
Usage: Mice were injected i.v. with CD117-SAP.
Related Products: Anti-CD117-SAP (Cat. #IT-83)