Researchers in the US have developed a new nanorobotic device based on DNA that can deliver “cargo”, such as drugs, to individual biological cells. The technology might one day be used to treat various diseases by directly programming the immune response of cells.

The nanorobot, developed by Shawn Douglas and colleagues of the Wyss Institute for Biologically Inspired Engineering at Harvard University, US, is in the form of a hexagonal DNA “hinged” barrel that can be opened and closed. The device measures 35 × 35 × 45 nm and can hold various types of cargo – such as metal nanoparticles – in its interior. It is kept closed by two “locks” that are encoded with aptamers – artificial nucleic-acid receptor molecules that bind to specific target molecules, like some antigens – and can be opened like an oyster shell when it interacts with the right combination of antigen “keys”. These keys can be proteins on biological cell surfaces and can be made to include specific disease markers, explains Douglas.

Logical locks

The nanorobot can be programmed to open when exposed to a single type of key by using the same aptamer sequence on both lock sites. Another possibility is to encode different aptamer sequences in the locks to recognize two inputs. Both locks need to be opened at the same time to activate the device and it remains firmly shut if only one of the two locks is opened. The lock mechanism thus functions as a logical AND gate: cell-surface antigens either bind (“0”) or do not bind (“1”) to aptamer locks.

The barrel was made using “DNA origami” in which complex 3D shapes and objects are constructed by folding strands of DNA. Such a technique has already been used to make nano-sized boxes, which are also capable of carrying cargo, with lids that can be locked and unlocked.

“When the nanorobot opens, its previously sequestered biologically active payload can then interact with nearby cells,” explains Douglas. “By designing the lock to open when bound to a particular antigen available on a cell surface, the device can thus be targeted to induce cell-signalling ‘instructions’ in certain cell populations that express the antigen. At the same time, the cargo is prevented from interacting with other cells [that do not express the antigen] in the same environment.”

Instructing cancer cells

The researchers have already used their device to deliver instructions, encoded in antibody fragments, to two different types of cancer cells – those responsible for leukaemia and lymphoma. “The instructions were different for both types of cancer cell and contained different antibody combinations,” explains Douglas, “and in each case, the message was to activate the cells’ ‘suicide switch’ – a standard feature that allows ageing or abnormal cells to destroy themselves.”

The device is the first DNA-origami-based system that employs antibody fragments to convey molecular instructions, something that allows for a completely controlled and programmable way to replicate an immune response, says team leader, George Church. “We are now finally able to integrate sensing and logical computing functions via complex, yet predictable nanostructures,” he states. “These are some of the first hybrids of structural DNA, antibodies, aptamers and metal atomic clusters aimed at useful, very specific targeting of human cancers.”

The team now plans to test its device on rodents before considering human clinical trials. “Its applications are possibly not just restricted to smart therapeutics but may also be used in diagnostics and even nonmedical applications,” adds Church.

The work was published in Science 10.1126/science.1214081.