Targeted Gene Therapy Using Synthetic Vectors

DESCRIPTION (provided by applicant): Gene therapy is a promising approach for treatment of human diseases rooted in genetic disorders (e.g., cancer). However, a major obstacle in the application of gene therapy as a viable treatment modality is the development of safe and effective gene transfer vectors. Both viral and non-viral (synthetic) vectors are actively being studied. To date, viral vectors have been studied much more than synthetic vectors. However, as research progresses, synthetic vectors are presenting themselves with several advantages over viral vectors. The goal of this proposed effort is to develop a new non-viral, targeted, gene transfer vector for gene therapy of neoplastic diseases. For the Phase I proof-of-principle, we have chosen folic acid as a targeting moiety for folate receptor expressing ovarian cancer cell model for in vitro experiments. Our novel gene transfer vectors will be evaluated for the potential treatment of ovarian cancer by conducting a series of in vitro assessments to characterize the vectors and determine the relative gene transfer efficiency of two reporter genes. We will screen vectors for DNA condensation, complex stability, and in vitro gene transfer. Ovarian cancer is the second most common and the deadliest gynecologic malignancy in the US. According to the American Cancer Society, ovarian cancer occurs at a frequency of ~23,000 new cases per year with a less than 50% survival rate. Existing treatment modalities for ovarian cancer have limited success rates due to difficulties in early detection and the progressive nature of the disease. Gene therapy, either used alone or in combination with other therapeutic modalities, provides new promises for effective control of cancers that are refractory to conventional therapeutic regimens. A new cancer-targeting gene tranfer agent based on a nanoparticle lipid-like scaffold as proposed here would be a welcome addition to the growing arsenal of cancer therapies.