Engineering exosome-mediated delivery of nucleic acids to treat breast cancer

The central goal of this project is explore a new therapeutic strategy for delivering therapeutic mRNA to breast cancer cells by harnessing exosomes – nanoscale vesicles that exhibit promising properties for delivery of therapeutics to cancer cells. In preliminary work, we demonstrated that exosomes may be harnessed to deliver mRNA to prostate cancer cells, and that these recipient cells translate this mRNA into substantial amounts of protein. We have also developed a strategy for enhancing exosome uptake by cancer cells by engineering proteins displayed on the surface of exosomes. Building on this foundation, we propose to investigate whether exosomes may be harnessed to delivery therapeutically relevant mRNA to breast cancer cells. Cargo mRNA to be evaluated will encode the tumor suppressor proteins p53 and PTEN or an enzyme that converts a pro-drug to a toxic drug. This investigation will evaluate the feasibility of this mode of delivery, will investigate several strategies for enhancing exosome-mediated delivery of mRNA, and will evaluate whether exosome-mediated delivery of tumor suppressor mRNA can mediate therapeutically relevant responses in established cell lines representing both normal and malignant breast tissue. Altogether, this project will establish a foundation for subsequent in vivo evaluations of this novel therapeutic strategy.