Cell membranes before (left) and after nanotube spearing. Photograph: Courtesy of Zhifeng Ren

A team including four Boston College scientists has invented a technique that uses nanotechnology and magnetic fields to introduce foreign DNA into living cells. The procedure offers applications to biological research and, in the long run, the researchers hope, to medicine.

The groundbreaking technique, called carbon nanotube spearing, is described in the June issue of Nature Methods, an offshoot of the prestigious journal Nature, in an article whose nine coauthors include biology professors Thomas Chiles and Jennifer Mataraza ’94, Ph.D.’01, and physics professors Krzysztof Kempa and Zhifeng Ren.

In the new technique, DNA molecules are chemically bonded to specialized nanotubes, tiny cylindrical structures made up, in this case, of carbon and nickel molecules, with the nickel concentrated at one end. The nanotubes are then placed in a solution with target cells and subjected to a rotating magnetic field—one that changes direction many times per second—followed by a static magnetic field. When the rotating magnetic field is applied, the DNA-bearing nanotubes pierce the walls of cells. The static field drives the tubes, which are one-30th the diameter of a human hair, further in, until they penetrate cell nuclei.

The idea for nanotube spearing came out of a series of informal wine-and-cheese events that bring together the University’s biology and physics departments to hear “chalk talks” by fellow professors on their current research. At a spring 2004 gathering, Krzysztof Kempa discussed his work with nanotubes. Kempa and some colleagues had been experimenting with the tubes as a way to ferry DNA into cells, using a line of tumor cells, recalls Thomas Chiles.

According to Chiles, Kempa said he was looking for biologists who might apply the spearing technique in their own research. “I perked up,” says Chiles, who studies B-lymphocytes, a kind of white blood cell.

One of the long-standing obstacles to B-lymphocyte research, Chiles explains, has been the difficulty of introducing foreign DNA—which, by interfering with the host cells’ processes, can add to knowledge about their normal functioning. At the time of Kempa’s talk, the main techniques for delivering DNA were either grossly inefficient—that is, they delivered DNA to only a few of the target cells—or they sent the DNA in on the backs of viruses that could deform or kill the cells they penetrated.

Shortly after Kempa’s talk, Dong Cai, a researcher at NanoLab, a Newton-based company whose founders and principal owners include Kempa and Zhifeng Ren, appeared at Chiles’s Higgins Hall laboratory bearing nanotubes and electromagnets. In the collaboration, Chiles and Mataraza supplied a “marker” DNA that causes cells to fluoresce when it penetrates them; several kinds of target cells, including lymphocytes and neurons from live mice and samples from standard laboratory cell lines; and the equipment to measure whether the cells had been penetrated and, if so, how well they had survived the process.

Months of work followed, with the researchers trying out various lengths and concentrations of nanotubes and strengths of magnetic fields for varying durations. Nanotube spearing, says Ren, “is just like archery. You don’t want to shoot [the nanotube] too fast or slow. If you shoot it too fast, it will destroy the cell. If you shoot it too slow, it will not penetrate.” Eventually the team figured out how to deliver DNA effectively to roughly 90 percent of target cells. According to Mataraza, no other technique has penetrated so many different types of cells with DNA so efficiently. She characterizes the project as an example of “how two departments that haven’t joined forces before can come up with results we can use in our labs on a daily basis.” NanoLab has applied for a patent on the process.

In the short run, nanotube spearing will likely be used principally for basic research. In the long run, the technique holds promise as a clinical means of correcting faulty genes or delivering medications directly to diseased cells. Ren reports that private biotechnology firms, as well as researchers in government and academe, have expressed interest.

The interdisciplinary approach employed in developing the delivery system represents the future of the natural sciences, says Chiles—“If you looked at physics, chemistry, and biology, there were very, very defined walls between them. But the walls are melting away.” He points to the National Institutes of Health, a major supporter of biological research, which is increasingly favoring collaborative projects across scientific disciplines. “A lot of places are already doing this,” Chiles says. “Now BC is on the train.”

David Reich is a writer based in the Boston area.

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