Many strategies for gene therapy of solid tumors such as prostate cancer have involved the use of Moloney murine leukemia (MLV)-based retroviral vectors, but gene transfer with standard replication-defective MLV vectors has not been efficient due to their low titers and limited diffusion into the tumor. Gene transfer using replication-competent retroviral vectors would be more efficient, as each successfully transduced tumor cell would itself become a virus-producing cell. We have devised a novel replication-competent MLV vector that has proven to be stable over at least 8 serial passages in cell culture, and is capable of highly-efficient gene delivery to solid tumors in vivo in a nude mouse xenograft model. Until now, the use of such replication-competent virus vectors has rarely been contemplated due to the risks associated with uncontrolled spread of replication-competent virus. We now propose to target these vectors specifically to prostate tumors by engineering the prostate-specific probasin promoter into the retroviral long terminal (LTR) to control transcription of the replication-competent retroviral RNA genome. Targeting the retrovirus specifically and exclusively to tumor cells would limit and control the replicative process and minimize the risk to normal cells, and would represent a significant improvement in vector design.
Targeted delivery of therapeutic genes for cancer treatment or gene replacement therapy.
