The Crucible Virus: A Viral Platform Based on HSV-1, Lentivirus, and Influenza Vectors for Regenerative Therapy and Cancer Targeting

Background: Safety and specificity remain major challenges in viral gene therapy for cancer and tissue repair. The Crucible Virus integrates replication deficient lentivirus, herpes simplex virus type one, and influenza A vectors into a single insulated chassis that enforces multi-input promoter gating and multi-tier kill switches to achieve conditional activation and enhanced safety. Methods: Vectors incorporate heat and cytokine responsive promoters HSP70 and NF kappa B, cHS4 insulators, and unique DNA barcodes. In vitro assays quantified promoter induction, basal leak, and engagement of CRISPR Cas nine and protease cleavable degron kill switches. Seven orthotopic and xenograft tumor models received sequential or combined dosing via intravenous and intralesional routes with assessments of biodistribution, immunogenicity, survival, and tumor volume. Results: The HSP70 and NF kappa B promoters achieved up to 168-fold induction with less than 0.2 percent basal leak. Off target CRISPR excision removed more than 90 percent of the payload within ninety minutes, and degron clearance reduced secreted effectors by half in under one hour. Median survival improved by thirty to sixty percent with probability value less than 0.01, and tumor volumes shrank by forty to fifty two percent compared to controls. Vector genomes cleared to below five thousand copies per microgram DNA by day twenty-eight, with off target activation under 0.5 percent and manageable antibody titers. Conclusions: The Crucible Virus delivers robust antitumor efficacy and regenerative potential under rigorous safety controls. Its modular traceable design supports scalable manufacturing and an investigational new drug ready profile for precision oncology and regenerative medicine applications.