Development of Targeted Sindbis Virus Vectors for Potential Application to Breast Cancer Therapy
JOHNS HOPKINS UNIV BALTIMORE MD SCHOOLOF MEDICINE
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Two main challenges of cancer gene therapy are the development or vectors targeted specifically to tumor cells and the efficient delivery of the therapeutic agent to all or to the majority of tumor cells. Addressing these two issues, we intend to develop Sindbis virus SV, an alphavirus, into a novel vector for breast cancer gene therapy. The advantages of SV vectors include lack of serious disease caused by SV in humans, the ability of SV to infect nondividing and dividing cells, no risk of insertional mutagenesis because SV is an RNA virus, and the ability to produce high titer stocks and achieve high level of heterologous gene expression. Since SV kills cells by apoptosis, specific destruction of tumor cells will occur if the virus is targeted to tumor cells. Furthermore, use of a propagation-competent viral vector will provide a very efficient means of obtaining access to most or all of the tumor cell population. The long-term goal of this proposal is to develop target-specific SV vectors for application to breast cancer therapy by modifying the SV E2 envelope glycoprotein with ligands that recognize specific cell surface receptors on breast cancer tumors.
- Medicine and Medical Research