Foamy virus vectors for suicide gene therapy

Abstract

To improve the delivery of so-called suicide genes into tumors, recombinant retroviruses were constructed by inserting the herpes virus type 1 (HSV-1) thymidine kinase (tk), the E. coli cytosine deaminase (cd) and polynucleoside phosphorylase (pnp), or the jellyfish gene for the green fluorescent protein (gfp) into a foamy virus (FV)-derived replication-competent vector (pFOV-7). Expression and stability of the inserted foreign gene was analyzed by immunoblot and polymerase chain reaction (PCR). The functionality of the suicide genes was determined by a metabolic assay on virus vector infected cells and treatment with the respective prodrugs. In terms of vector stability and effectiveness of specific cell killing a virus transducing the pnp gene (FOV-7/pnp) was superior to those using the other two suicide genes. FOV-7/pnp is a candidate virus for suicide gene delivery into solid tumors.