Tiny "bubbles" may deliver genes to help fight diabetes, researchers say. Their experiments in rats have shown that this method can deliver insulin genes specifically to the pancreas, where insulin is needed.
The team injected microscopic spherical shells into rodents, and using a directed ultrasonic pulse they caused the bubbles to break and release their genetic contents in the target organ.
“I think this is a very useful technique for gene delivery and, as the authors stated, can be used to deliver other therapeutic agents as well,” says Jim Hu of the Hospital for Sick Children in Toronto, Canada, who was not involved with the study.
Gene therapy, the idea that DNA can be inserted into people’s cells to help them overcome disease, has a controversial history. The death of 18-year-old Jesse Gelsinger in 1999 raised alarm as the teenager was receiving gene therapy for a rare liver disorder. He appeared to suffer a severe immune reaction.
Hard to reach
Experts say that many challenges exist to making gene therapy work, including figuring out the best way to deliver the DNA therapy. Some types of gene therapy rely on using harmless viruses engineered to carry the healthy gene. When injected into an animal, the virus integrates itself – and the healthy gene – into the host’s DNA. But these viruses do not get to some of the most hard-to-reach cells in internal organs.
This problem matters a tremendous amount with regard to diabetes, in which the secretion or action of insulin is disrupted, says Mark Kay at the Stanford University School of Medicine in California, US.
He says that the cells producing important proteins – such as insulin – lie inside remote structures in the pancreas organ, which itself sits beneath the stomach. It is difficult for foreign particles – such as gene-therapy viruses – to get there from the blood.
Hypoglycaemic shock
Without a more sophisticated and targeted approach, cells throughout the body might pick up the gene and begin producing insulin. Since only pancreatic cells are fine-tuned to release insulin in response to food, other cells would over-produce the protein with no regard to food intake.
“The results would be willy-nilly – you’d more likely die from hypoglycaemic shock than the high blood sugar levels” that characterise diabetes, explains Kay.
For this reason, Paul Grayburn of Baylor University Medical Center in Texas, US, and his colleagues explored the use of microscopic bubbles, burst with a targeted pulse, to deliver insulin genes specifically to the pancreas. They injected the bubbles, which had a shell made of water-insoluble molecules, into rats. In initial experiments, the bubbles contained a plasmid – a piece of circular DNA – which only coded for a florescent protein marker.
Transient effect
Researchers directed an ultrasonic pulse at the pancreas of the rats to burst the tiny bubbles, releasing the genetic contents. When they later dissected the rats and examined their organs, they found there were higher levels of fluorescence in pancreatic tissue than in other tissues.
In the second part of the experiment, the bubbles contained plasmids with the human gene for insulin. The ultrasonic pulse was similarly directed towards each rat’s pancreas, and researchers later found significantly elevated levels of human insulin in the rodents.
But experts stress that this approach to introducing a healthy foreign gene, or “transgene”, does not offer a permanent fix because the circular DNA does not last. “Since the authors used plasmids for delivery in this study, only transient transgene expression was demonstrated,” says Hu.
Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0602921103)
