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d10-deficient vaccinia virus is a genetically engineered form of vaccinia virus in which the D10R gene, encoding the D10 decapping enzyme, has been deleted or inactivated. The D10 enzyme removes the 5’ cap structure from host and viral mRNAs, promoting their degradation and impeding host antiviral responses. D10-deficient vaccinia viruses show reduced virulence and attenuated pathogenesis in animal models. ΔD10 viruses replicate efficiently in tumor cells but are strongly attenuated in non-tumor cells due to their inability to degrade host mRNA and counteract innate immune responses such as PKR activation. This attenuation, combined with preferential replication in cancer cells, positions d10-deficient vaccinia virus as a promising oncolytic virus therapy. Enhanced safety profile arises from host restriction and reduced systemic toxicity. Anti-tumor efficacy has been demonstrated in murine models of breast cancer and in human hepatocellular carcinoma xenografts, where ΔD10 VACV reduced tumor volume and increased necrosis.
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