Simultaneous delivery of cancer treatment programs to tumor and immune cells

A herpesvirus population comprising:

• (i) a replication-competent herpesvirus comprising a cancer cell state classifier, wherein the cancer cell state classifier comprises:
• (a) a cancer cell sensor circuit comprising a first constitutive promoter operably linked to a nucleic acid encoding:
• (1) one or more target sequences for a first set of cancer input miRNAs;
• and
• (2) a nucleic acid sequence encoding one or more of a first set of repressors;
• and
• (b) a cancer cell signal circuit comprising a first subgenomic promoter operably linked to a nucleic acid encoding:
• (1) one or more of a first set of output molecules;
• and
• (2) a first repressor recognition sequence that is capable of being bound by the first repressor, wherein the first repressor is capable of binding to the first repressor recognition sequence to prevent expression of the first set of output molecules;
• (ii) a replication-deficient herpesvirus comprising an immune cell state classifier, wherein the immune cell state classifier comprises:
• (a) an immune cell sensor circuit comprising a second constitutive promoter operably linked to a nucleic acid encoding:
• (1) one or more target sequences for a first set of immune cell input miRNAs;
• and
• (2) a nucleic acid sequence encoding one or more of a second set of repressors;
• and
• (b) an immune cell signal circuit comprising a second subgenomic promoter operably linked to a nucleic acid encoding:
• (1) one or more of a second set of output molecules;
• and
• (2) a second repressor recognition sequence that is capable of being bound by the second repressor, wherein the second repressor is capable of binding to the second repressor recognition sequence to prevent expression of the second set of output molecules.