Grant: Operating Grant

Gene therapy offers the promise of a permanent cure for a wide range of disorders. The ability to permanently replace defective or missing genes is desirable over the current pharmacological interventions, which typically treat the disease symptoms but do little to eradicate the underlying cause. Successful gene reconstitution depends on the use of gene carriers. Naturally-occurring viruses act as effective gene carriers; however, they are not safe since they cause excessive immune reaction and sometimes cause uncontrolled tissue growth. As an alternative to viral carriers, this project will focus on designing gene carriers based on polymers. Polymers are relatively safe, since they are not capable of inserting the DNA molecules haphazardly into the normal genome. However, they are toxic on the cells and they are not very effective in transporting genes into the cells. This project aims to overcome these impediments of the polymeric gene carriers by preparing polymers that (1) can deliver a large amount of genes into cells and (2) do not display toxicity on the cells. The polymers will be synthesized form positively charged groups that can interact with negatively charged genes, and lipid molecules that can effectively transport genes into the cells. By engineering the right combination of positively charged with lipid groups, we will optimize the effectiveness of carriers for modification of human cells. Successful completion of this project will ultimately accelerate clinical practice of gene therapy.