Harvard Researchers Develop DNA Nanorobot to Trigger Targeted Treatment

Image Source: Wyss Institute

Scientists at Harvard University’s Wyss Institute for Biologically Inspired Engineering have developed a nanorobotic device made from DNA that could potentially seek out specific cell targets within a complex mixture of cell types and deliver important molecular instructions, such as telling cancer cells to self-destruct.

Inspired by the mechanics of the body’s own immune system, the technology might one day be used to program immune responses to treat various diseases. The study is published in Science.

Using the DNA origami method  (complex 3-D shapes and objects are constructed by folding strands of DNA), the researchers created a nanosize robot in the form of an open barrel whose two halves are connected by a hinge.

The nanorobot’s DNA barrel acts as a container that can hold various types of contents, including specific molecules with encoded instructions that can interact with specific signaling receptors on cell surfaces, including disease markers.

The barrel is normally held shut by special DNA latches. But when the latches find their targets, they reconfigure, causing the two halves of the barrel to swing open and expose its contents, or payload.

The researchers used this system to deliver instructions, encoded in antibody fragments, to two different types of cancer cells: leukemia and lymphoma.

In each case, the message to the cell was: activate your apoptosis or “suicide switch” — which allows aging or abnormal cells to be eliminated.

This programmable nanotherapeutic approach was modeled on the body’s own immune system, in which white blood cells patrol the bloodstream for any signs of trouble.

These infection fighters are able to home in on specific cells in distress, bind to them, and transmit comprehensible signals to direct them to self-destruct. This programmable power means the system has the potential to one day be used to treat a variety of diseases.

“We can finally integrate sensing and logical computing functions via complex, yet predictable, nanostructures — some of the first hybrids of structural DNA, antibodies, aptamers, and metal atomic clusters — aimed at useful, very specific targeting of human cancers and T-cells,” said George Church, a Wyss core faculty member and professor of genetics at Harvard Medical School, who is principal investigator on the project.

Because DNA is a natural biocompatible and biodegradable material, DNA nanotechnology is widely recognized for its potential as a delivery mechanism for drugs and molecular signals.

There have been significant challenges to its implementation, such as what type of structure to create; how to open, close, and reopen that structure to insert, transport, and deliver a payload; and how to program this type of nanoscale robot.

“This work represents a major breakthrough in the field of nanobiotechnology as it demonstrates the ability to leverage recent advances in the field of DNA origami pioneered by researchers around the world, including the Wyss Institute’s own William Shih, to meet a real-world challenge, namely killing cancer cells with high specificity,” said Wyss Institute Founding Director Donald Ingber.

Payloads such as gold nanoparticles (gold) and antibody fragments (magenta) can be loaded inside the nanorobot.

DNA nanorobot from Wyss Institute on Vimeo.

Wyss Institute