Researchers Do Precise Gene Therapy without a Needle

By Pam Frost Gorder

For the first time, researchers have found a way to inject a precise dose of a gene therapy agent directly into a single living cell without a needle.

The technique uses electricity to “shoot” bits of therapeutic biomolecules through a tiny channel and into a cell in a fraction of a second. L. James Lee and his colleagues describe the technique in Nature Nanotechnology, where they report successfully inserting specific doses of an anti-cancer gene into individual leukemia cells to kill them.They have dubbed the method “nanochannel electroporation,” or NEP. 

“NEP allows us to investigate how drugs and other biomolecules affect cell biology and genetic pathways at a level not achievable by any existing techniques,” said Lee, who is the Helen C. Kurtz Professor of Chemical and Biomolecular Engineering and director of the NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices at Ohio State.

Lee invented the technique for forming strands of DNA into precise patterns so that they could work as wires in biologically based electronics. But for this study, gold-coated DNA strands were stretched between two reservoirs and then etched away, in order to leave behind a nano-channel of precise dimensions connecting the reservoirs within the polymeric device.

To test whether NEP could deliver active therapeutic agents, they inserted bits of therapeutic RNA into leukemia cells. Pulses as short as 5 milliseconds delivered enough RNA to kill some of the cells. Longer pulses — approaching 10 milliseconds — killed almost all of them. They also inserted some harmless RNA into other leukemia cells for comparison, and those cells lived. At the moment, the process is best suited for laboratory research, Lee said, because it only works on one cell or several cells at a time. But they are currently developing a mechanical cell-loading system that would inject up to 100,000 cells at once, which would potentially make clinical diagnostics and treatments possible.

Featured in the photograph with Lee is Daniel Gallego-Perez. Daniel joined Dr. Lee’s group in July, after the development of this technology. Daniel is currently a Postdoctoral Researcher at the NSF Nanoscale Science and Engineering Center (NSEC), and an Associate Staff member for Nanotech West at Ohio State. Daniel is currently working on trying to use this new technology to characterize better cancerous cells.

In June 2011, Daniel completed his Ph.D. in Biomedical Engineering here at Ohio State for his dissertation titled “Micro/nanoscale Engineering of the Cell Microenvironment.”  BME Professor Derek Hansford was his Ph.D. advisor and Dr. Keith Gooch co-advised part of his research. His work focused on using micro and nanoscale technologies to manipulate the cellular microenvironment and control cell behavior. This concept was studied in a number of areas of relevance to biomedical engineering, including tissue engineering, cell therapy and implant surface engineering among others.

Read more details from the Office of Research.