Foamy virus vectors for suicide gene therapy.
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.
Nestler
U
U
Institut für Virologie und Immunbiologie, Universität Würzburg, Germany.
Heinkelein
M
M
Lücke
M
M
Meixensberger
J
J
Scheurlen
W
W
Kretschmer
A
A
Rethwilm
A
A
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D043525:Cytosine Deaminase; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D009700:Nucleoside Deaminases / Q000235:genetics; D016133:Polymerase Chain Reaction; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics; D016092:Spumavirus; D013937:Thymidine Kinase / Q000235:genetics
D011683:Purine-Nucleoside Phosphorylase; D013937:Thymidine Kinase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase