This project will conduct experiments to optimize the design and delivery of therapeutic oligonucleotide agents targeted to the STAT3 pathway. STAT3 is a transcription factor central to the up-regulation of many genes involved in lymphoma cell survival, proliferation and resistance to therapy. STAT3 inhibition will both directly target tumor cells as well as curtail the suppression of the normal anti-tumor immune response in the cells of the tumor microenvironment. One agent, pG-STAT3siRNA, is currently being tested for animal toxicology to prepare for human clinical trials.
The specific aims of this project are as follows:
Aim 1: Develop anti-lymphoma targeting of oligonucleotide-conjugated STAT3 siRNA delivery systems.
Aim 2: Optimize CpG-STAT3dODN strategy for targeting B cell lymphoma cells