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oHSV-shPKR is a novel oncolytic Herpes simplex virus (oHSV) engineered to express a short hairpin RNA (shRNA) targeting the protein kinase R (PKR) signaling pathway. By silencing tumor-intrinsic PKR, which is a key component of the host's antiviral defense, the virus enhances its own replication and lytic potential within glioblastoma (GBM) cells, including those resistant to standard oncolytic viruses. Beyond direct oncolysis, oHSV-shPKR modulates the tumor microenvironment by inducing G2/M cell cycle arrest and activating antigen-presenting cells through type I interferon signaling. This immune-stimulatory effect promotes the expansion of tumor-antigen-specific CD8+ T cells and cytotoxic T lymphocytes. Developed by researchers at the University of Texas Health Science Center at Houston, oHSV-shPKR has demonstrated preclinical efficacy in patient-derived xenograft and immunocompetent murine models of glioblastoma.
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