Grant: Foundation Grant

Current drugs suffer from two major limitations. First, they go everywhere in the body and only a small proportion arrives at a disease site such as a cancerous tumour. This results in toxic "side effects" due the effects of the drug on healthy tissue, as well as limited potency. Second, most drugs used today are "small molecules" that are small enough to penetrate into cells in the body to affect disease. The ability to use larger "genetic" drugs based on RNA and DNA to enable genetic therapies would have revolutionary consequences. Such drugs use natural regulatory processes in the body to treat disease leading to new potential treatments for most human diseases. The goal of this project is to develop "smart" nanomedicines that target small molecule drugs more accurately to disease sites and that enable genetic drugs to be used as therapeutics. These smart nanomedicines consist of the drug encapsulated into a nanoparticle that is administered by intravenous injection. These nanoparticles have dimensions of 100 nm or less, approximately 100 times smaller than a cell in the body. They are therefore able to permeate through most tissues and can be readily accumulated by most cells in the body. Specific goals of the project are to: 1) Development of triggered release lipid nanoparticle (LNP) systems to release therapeutic concentrations of small molecule drugs at sites of disease; 2) Development of LNP systems to extend applications of genetic drugs to extra-hepatic tissues; 3) Development of LNP systems containing genetic drugs that are not immunogenic; 4) Demonstrate efficacy of LNP systems in animal models of osteoporosis, diabetes, inflammation, neurological disorders, prostate cancer and leukemia. This research program builds on a strong record in drug development, as well as a well-established interdisciplinary network of collaborators in academia and industry.