Systemic gene therapy by Sindbis vectors: A potentially safe and effective targeted therapy for identifying and killing tumor cells in vivo.

Extract: A major obstacle to the development of gene therapy for cancer has been the inability to specifically and systemically deliver gene therapy vectors throughout the body to primary and/or metastasized tumor cells. Although intratumor injections of gene therapy vectors have sometimes been possible, no viral vector has been available that could be administered systemically and would selectively and efficiently target tumors without infection of normal tissues. Furthermore, even when locally injected, many viral vectors end up at high concentrations in the liver, because many cells of the body have low receptor numbers for some of the vectors in current use, whereas the liver has high numbers of such receptors. A number of ingenious approaches have been tried but none so far have fully resolved the problem. For example, tumor-specific promoters have been incorporated into the vectors so that gene expression and/or replication can occur in tumor cells but not normal cells. Unfortunately, only a small fraction of these vectors are typically taken up by the target tumor and expressed. In such cases, tumor cell death is generally insufficient to eradicate or significantly slow tumor growth.