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IL-13Rα2-targeted extracellular vesicles with CRISPR-Cas9 is an experimental gene-editing therapeutic platform developed by researchers at the University of California San Diego for the treatment of idiopathic pulmonary fibrosis (IPF). The therapy utilizes engineered small extracellular vesicles (sEVs) to deliver CRISPR-Cas9 components directly to cells expressing the IL-13Rα2 receptor, which is upregulated in fibrotic lung tissue. The sEVs are engineered by modifying the tetraspanin CD63 with an MS2 RNA-binding protein to facilitate the loading of guide RNAs (gRNAs) expressing MS2. These vesicles package Cas9 and gRNAs as a ribonucleoprotein (RNP) complex via MS2–MCP RNA–protein interactions. By targeting and knocking down the *IL13RA2* gene, the therapy suppresses profibrotic TGF-β1 signaling via the AP-1 axis, reduces epithelial-mesenchymal transition (EMT), and decreases extracellular matrix accumulation, leading to functional recovery in preclinical models.
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