Grant: Project Grant

Acute myeloid leukemia (AML) is an aggressive blood cancer with low survival rates and high burden of treatment side effects. There is a growing list of promising gene targets, such as transcription factors, in which their activation may have a potent therapeutic effect. However, most new drugs and novel therapeutic approaches for AML act by inhibiting targets. In this project, a diverse team of three research groups from Pharmacology & Therapeutics, Chemistry, and Medicine will develop new RNA molecules as potential therapeutics that activate expression of specific genes for curing AML patients with otherwise poor prognosis. Specifically, we will design, synthesize, screen, and characterize chemically-modified, duplex RNAs that tune the expression of transcription factors via a novel RNA activation mechanism. These new RNA drugs will be delivered specifically to the leukemia cells using lipid nanoparticles, to improve the safety and efficacy of the treatment. Indeed, our preliminary results show selective delivery of RNA to leukemia cells, increased target gene expression, and lower AML disease burden in animals. We will evaluate the safety and potential therapeutic impact of our RNA molecules to treat AML in validated cell and animal models. As a result of extensive collaborations already in place, promising candidates from this project will have a clear path forward into clinical development.