Targeted Therapy for Neoplastic Diseases

Ovarian cancer is a serious threat and ranks among the top leading causes of cancer deaths among women in the United States. Ovarian cancer is normally considered to be the result of genetic alterations. Therefore, gene therapy offers a promising approach for the treatment of ovarian cancer. Herein we propose to combine nanotechnology and the nonviral sleeping beauty transposon-based gene transfer system to develop safe and effective nanotransposon particles (NTPs) that could achieve targeted delivery of a DNA-based drug to cancer cells for treatment of ovarian cancer. TransGenex has developed a novel nanogene delivery approach using NG042, a novel chitosan nanoparticle, to effectively deliver DNA plasmids or peptides through intranasal or oral routes. We have also identified a novel natriuretic peptide, NP731-102, as a candidate drug for treatment of ovarian cancer. Preliminary data has shown that NP73-102 overexpression induces apoptosis and decreases the development of lung tumors in nude mice and of subcutaneous tumors in an immunocompetent syngeneic mouse model. We propose to use NTPs to induce persistent expression of NP73-102 specifically in ovarian cancer cells and thus effectively treat ovarian cancer.