DNA origami nanorobot takes drug direct to cancer cell

How is this for a clever robot? Tiny probes built from DNA can seek and destroy cancer cells, leaving healthy cells untouched. These clam-like bots, which release their drug payload only when they reach and identify their target, could 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 modelling 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.

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 payload.

Collateral damage

To test its therapeutic potential, Douglas's team created a nanorobot with locks that unzipped in response to molecules expressed on the surface of leukaemia 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 leukaemia cells had been destroyed, but no healthy cells had been harmed.

Douglas reckons that by adding additional payloads to cripple more of the cells' normal functioning, his team could target every last one of the leukaemia cells. What's more, by altering the lock, the nanorobots could be designed to target any type of cell.

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.

Exquisitely targeted

J?rgen 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 is also hopeful. "Smart drugs which can be exquisitely targeted to specific cell types are a major goal of biomedical research," he says. "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."

Journal reference: Science, DOI: 10.1126/science.1214081

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