biostudies-literatureSuryawanshi YRNational Cancer InstituteMayo ClinicNCI NIH HHSNational Institutes of Health1-13https://www.ebi.ac.uk/biostudies/studies/S-EPMC8455367biostudies-literatureUnknown23A dual microRNA-detargeted oncolytic Mengovirus, vMC₂₄NC, proved highly effective against a murine plasmacytoma in an immunocompetent syngeneic mouse model; however, there remains the concern of escape mutant development and the potential for toxicity in severely immunocompromised cancer patients when it is used as an oncolytic virus. Therefore, we sought to compare the safety and efficacy profiles of an attenuated Mengovirus containing a virulence gene deletion versus vMC₂₄NC in an immunodeficient xenograft mouse model of human glioblastoma. A Mengovirus construct, vMC₂₄ΔL, wherein the gene coding for the leader protein, a virulence factor, was deleted, was used for comparison. The vMC₂₄ΔL induced significant levels of toxicity following treatmeMolecular therapy oncolyticsMicroRNA-detargeting proves more effective than <i>leader</i> gene deletion for improving safety of oncolytic Mengovirus in a nude mouse model.PMC8455367R01 CA207386Schulze AJNace RARussell SJSuryawanshi YRfalseMicroRNA-detargeting proves more effective than <i>leader</i> gene deletion for improving safety of oncolytic Mengovirus in a nude mouse model.A dual microRNA-detargeted oncolytic Mengovirus, vMC₂₄NC, proved highly effective against a murine plasmacytoma in an immunocompetent syngeneic mouse model; however, there remains the concern of escape mutant development and the potential for toxicity in severely immunocompromised cancer patients when it is used as an oncolytic virus. Therefore, we sought to compare the safety and efficacy profiles of an attenuated Mengovirus containing a virulence gene deletion versus vMC₂₄NC in an immunodeficient xenograft mouse model of human glioblastoma. A Mengovirus construct, vMC₂₄ΔL, wherein the gene coding for the leader protein, a virulence factor, was deleted, was used for comparison. The vMC₂₄ΔL induced significant levels of toxicity following treatme2021-01-01T00:00:00Z2021 Dec2026-05-07T20:23:33.144Z2022-02-11T11:43:46.087ZS-EPMC84553673458958010.1016/j.omto.2021.08.011