(478d) Liposomal siRNA Delivery to Silence Aromatase for Breast Cancer Treatment

Authors: 
Cavanaugh, M. L. - Presenter, The Ohio State University
Lee, L. J. - Presenter, the Ohio State University
Lee, R. J. - Presenter, the Ohio State University
Sugimoto, Y. - Presenter, The Ohio State University
Brueggemeier, R. W. - Presenter, The Ohio State University


Increased expression of certain genes is common in many diseases and inhibiting these over-expressed genes is an option for treating them. RNA interference is one such gene silencing technique and is a potentially very powerful approach to cancer therapy. This collaborative research effort seeks to develop a novel liposomal vector to successfully deliver siRNA that will suppress aromatase activity in tumor cells for breast cancer treatment. Aromatase is an enzyme that produces estrogens and the expression and activity of aromatase are higher in breast cancer cells than in normal breast tissue. Approximately 70% of breast cancers are estrogen receptor positive and the current first line treatment for postmenopausal women with these cancers is aromatase inhibitors. However, current aromatase inhibitors bring about estrogen deprivation in the entire body, causing some side-effects. Using siRNA targeting aromatase mRNA specific to breast cancer cells allows estrogen levels to be decreased in a tissue specific manner leading to diminished side-effects. Additionally, a liposomal drug delivery system will not only help prevent siRNA degradation, but can increase circulation time, target tumor cells, improve cellular uptake, and lower the required effective dose.