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shDDR1 is a short hairpin RNA (shRNA) construct designed to silence the expression of discoidin domain receptor 1 (DDR1), a collagen-binding receptor tyrosine kinase. In the context of glioblastoma (GBM), DDR1 is often overexpressed and plays a critical role in maintaining an immunosuppressive tumor microenvironment by promoting the alignment of collagen fibers and the formation of 'oncostreams'—multicellular structures that facilitate tumor cell invasion. By knocking down DDR1 expression, shDDR1 aims to remodel the extracellular matrix, enhance the infiltration of CD45+ and CD3+ immune cells into the tumor core, and increase the sensitivity of glioma cells to radiotherapy. Preclinical studies using the Sleeping Beauty transposase system in genetically engineered mouse models have demonstrated that DDR1 knockdown significantly prolongs median survival and reduces the presence of glioma-associated microglia.
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