Grant: Operating Grant: Industry-partnered Collaborative Research

Small interfering RNA (siRNA) oligonucleotides can efficiently and specifically "silence" the production of particular "target" proteins in cells by binding to the mRNA that codes for that protein. This results in a catalytic destruction of the targeted mRNA and thus the target protein is not made. The siRNA molecules against particular proteins have major potential as therapeutics. For example, targeting and silencing oncogenes that promote the growth of tumours should inhibit tumour growth. Alternatively, silencing proteins such as Apo- B, which is essential for formation of the low density lipoproteins, should inhibit the plaque formation associated with heart disease. However, siRNA molecules cannot currently be used as in vivo therapeutics because they are rapidly broken down in the circulation, do not accumulate at disease sites and cannot get into cells. Lipid nanoparticles (LNP) have been demonstrated to have potential as delivery systems to overcome these problems. However, the cationic (positively charged) lipids used in these systems can be toxic, the efficiency of accumulation at disease sites is low and intracellular delivery properties have not been optimized. The studies to be performed in this work are aimed at developing cationic lipids that have reduced toxicity and improved intracellular delivery properties and can be used to deliver siRNA to a variety of tissue types in the body.