DNA ‘nanorobot’ effectively targets cancer leaving healthy cells untouched: Study

By Dr. Ananya Mandal, MDFeb 20 2012

Researchers have developed ‘nano-sized’ probes built from DNA that can seek and destroy cancer cells, leaving healthy cells untouched. These ‘nanorobots’ release their drug payload only when they reach and identify their target and are believed to improve many treatments for disease.

Shawn Douglas and his colleagues at Harvard University's Wyss Institute have used “DNA origami” to build the nanorobot. The team designed the device with DNA modeling software that understands how DNA base pairs bind together, as well as the helical structure that results. When they enter a shape of their choosing into the program, it returns a list of DNA strands that can be mixed together to create the desired shape. The shape that Douglas and his colleagues had in mind was clam-like, so that the nanorobot could hold a drug dose inside until it was time to deliver it.

DNA is a material, shaped in the form of a revolving ladder, which carries the genetic information in our cells. The double-sided strands have so-called sticky ends that allow them to be joined together with other DNA. Scientists, led by Nadrian Seeman, now head of the Department of Chemistry at New York University, have used those sticky ends to form DNA into lattices that can be shaped in various ways.

To ensure that the clam only opened when it found its target, the team fitted the nanorobot with two locks. Each lock is a strand of DNA called an aptamer that can be designed to recognise a specific molecule. When the aptamer and target molecule meet, the DNA strand unzips, unlocking the clam and releasing the drug stored within.

To test its therapeutic potential, Douglas's team created a nanorobot with locks that unzipped in response to molecules expressed on the surface of leukemia cells. The team then loaded it with a single molecule known to kill cells by interfering with their growth cycle. Finally, they released millions of copies into a mixture of healthy and cancerous human blood cells. Three days later, around half of the leukemia cells had been destroyed, but no healthy cells had been harmed.

Having two locks means that a nanorobot is better able to distinguish diseased and healthy cells, says Douglas. “It would require that two different signals have to be present to open it, increasing its specificity,” he says. He hopes the cancer-targeting nanorobots can leave untouched other types of rapidly dividing cells, such as those in the gut and at hair follicles, that often suffer collateral damage during chemotherapy.

Jørgen Kjems at Aarhus University in Denmark agrees. “The group provide proof of principle that DNA origami has the capacity to create highly intelligent drugs that activate only on encountering diseased cells,” he says. “This will inevitably lower the toxicity and side effects of the drugs carried within the device.”

Paul Rothemund at the California Institute of Technology in Pasadena added, “Smart drugs which can be exquisitely targeted to specific cell types are a major goal of biomedical research…The ability to [match] the binding of the clam shell to the targeted cell type and use this as a trigger for delivery is a major step beyond the smart drugs of today.” “The next step will be to ensure the DNA nanorobot can withstand the destructive environment of living organisms,” says Kjems. “Once this has been accomplished, there's promise that scientists can create new and more effective medicines for animals and humans.”

The research is published in the journal Science. Dr Douglas said that there was still much optimization to be done on the robots; for now the team will create a great many of them to be tested in an animal model. Besides cancer, the robots may also benefit people with autoimmune disease, Douglas said. One day, the robots might be used to find immune cells wrongly attacking the body and reprogram them, he said.

“It’s an important step forward in specific targeting,” said Milan Stojanovic, an assistant professor of experimental therapeutics at Columbia University in New York who wasn’t involved in the research, in an e-mail. “It looks very exciting.”