DELIVERY OF THE P53 TUMOR-SUPPRESSOR GENE INTO LUNG-CANCER CELLS BY AN ADENOVIRUS DNA COMPLEX/

An adenovirus/DNA complex was constructed by chemically linking poly-L -lysine to the capsid of the replication-defective adenovirus dl312, a llowing for coupling with plasmid DNA by an ionic interaction. We have previously demonstrated that this adenovirus/DNA complex can efficien tly transduce malignant cells with a plasmid expressing the beta-galac tosidase gene both in vitro and in vivo. In this report, we show that this system can deliver a therapeutic gene that encodes for the tumor suppressor protein p53 to lung cancer cells, both in vitro and in vivo , leading to significant biological effects. Transfection of the p53-n egative human lung cancer cell line H1299 with the adenovirus/DNA comp lex carrying a plasmid expressing the p53 gene resulted in high levels of p53 protein and induction of apoptosis. Injection of the complex c arrying the p53 gene to subcutaneous tumor sites 5 days after tumor ce ll implantation resulted in a significant inhibition of tumorigenicity as measured by the number and size of tumors that developed 21 days a fter treatment. Three and six injections of the complex carrying the p 53 gene into H1299 subcutaneous tumor nodules led to significant dose- related tumor growth suppression 18 days after the first injection com pared with control-treated tumors. This adenovirus/DNA complex, theref ore, is capable of efficiently delivering the p53 gene into malignant cells in vitro and in vivo and now provides a general gene delivery ve ctor that is simple to construct and capable of testing therapeutic ge nes in malignant cells.