biostudies-literatureUnknown28Penza VMengovirus is an oncolytic picornavirus whose broad host range allows for testing in immunocompetent cancer models. Two pathogenicity-ablating approaches, polycytidine (polyC) tract truncation and microRNA (miRNA) targets insertion, eliminated the risk of encephalomyocarditis. To investigate whether a polyC truncated, miRNA-detargeted oncolytic Mengovirus might be boosted, we partially or fully rebuilt the polyC tract into the 5' noncoding region (NCR) of polyC-deleted (MC₀) oncolytic constructs (NC) carrying miRNA target (miRT) insertions to eliminate cardiac/muscular (miR-133b and miR-208a) and neuronal (miR-124) tropisms. PolyC-reconstituted viruses (MC₂₄-NC and MC₃₇-NC) replicated <i>in vitro</i> and showed the expected tropism restrictions, but reducedMolecular therapy oncolytics15-30https://www.ebi.ac.uk/biostudies/studies/S-EPMC9800256biostudies-literaturePolycytidine tract deletion from microRNA-detargeted oncolytic Mengovirus optimizes the therapeutic index in a murine multiple myeloma model.PMC9800256Penza VSchulze AJNace RARussell SJMaroun JWfalsePolycytidine tract deletion from microRNA-detargeted oncolytic Mengovirus optimizes the therapeutic index in a murine multiple myeloma model.Mengovirus is an oncolytic picornavirus whose broad host range allows for testing in immunocompetent cancer models. Two pathogenicity-ablating approaches, polycytidine (polyC) tract truncation and microRNA (miRNA) targets insertion, eliminated the risk of encephalomyocarditis. To investigate whether a polyC truncated, miRNA-detargeted oncolytic Mengovirus might be boosted, we partially or fully rebuilt the polyC tract into the 5' noncoding region (NCR) of polyC-deleted (MC₀) oncolytic constructs (NC) carrying miRNA target (miRT) insertions to eliminate cardiac/muscular (miR-133b and miR-208a) and neuronal (miR-124) tropisms. PolyC-reconstituted viruses (MC₂₄-NC and MC₃₇-NC) replicated <i>in vitro</i> and showed the expected tropism restrictions, but reduced2023-01-01T00:00:00Z2023 Mar2025-04-04T12:37:29.288Z2025-04-04T12:37:29.288ZS-EPMC98002563661929310.1016/j.omto.2022.11.006