Delivering DNA sequences to cells for gene therapy is already being investigated, with the current approaches relying on viruses and smart nanoparticles as vectors for gene transfers. But Philips and GlyGenix Therapeutics, out of Woodbridge, CT, plan on taking another approach, hoping that the large molecules can be pushed to their destination using ultrasound. Specifically, the pre-clinical trials will study the technology, known as ultrasound-mediated plasmid DNA (pDNA) delivery, on Glycogen Storage Disease Type 1a (GSD-1a) that exhibits a defective G6Pase gene.
Current gene therapies that rely solely on the bloodstream to deliver corrective gene molecules typically fail to deliver sufficient quantities to the target organs. However, by directing focused ultrasound to target organs following DNA delivery, an increase in uptake via a process known as sonoporation has been successfully demonstrated in pre-clinical studies. Sonoporation increases the permeability of cell walls to allow the uptake of large molecules, thereby enabling the delivery of therapeutic genes.
Compared to current gene therapies that use viral vectors to infect cells, this ultrasound-mediated technique carries no risk of an anti-viral immune or inflammatory response. In addition, this targeted approach could reduce side effects.
The proposed treatment is known as ultrasound-mediated plasmid DNA (pDNA) delivery. The research program into it will specifically target the expression of a functional human G6Pase therapeutic pDNA to the liver, the primary organ responsible for glycogen storage and glucose release. Pre-clinical studies to investigate the feasibility of the technique will be carried out by Philips Research and GlyGenix Therapeutics in collaboration with the Duke University School of Medicine’s Division of Medical Genetics (Durham, North Carolina, USA) – a recognized leader in GSD-1a diagnosis, managed care, pediatric genetics and experimental models.