The researchers said in a press release they were inspired by the mechanics of the body’s immune system. The technology may some day be used to program immune responses to treat various diseases, they wrote in today’s issue of Science.
“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,” George Church, a Wyss faculty member and principal investigator on the project, said in a statement.
Using the DNA origami method, in which complex three-dimensional shapes and objects are constructed by folding strands of DNA, the researchers created a nanosized robot that looks like an open barrel with its halves connected by a hinge. The DNA barrel, which acts as a container, is held shut by special DNA latches that can recognize and seek out combinations of cell-surface proteins, including disease markers. When the latches find their targets, they reconfigure, causing the two halves of the barrel to swing open and expose the contents or “payload.” The container can hold various types of payloads, including certain molecules with encoded instructions that can interact with specific cell surface signaling receptors.
The scientists used the system to deliver instructions, which were encoded in antibody fragments, to two different types of cancer cells, leukemia and lymphoma. Both cell types were instructed to activate their suicide switch, a naturally occurring feature that allows aging or abnormal cells to be eliminated in a process called apoptosis. Because leukemia and lymphoma cells essentially speak different languages, the messages were written in different antibody combinations.
The programmable nanotherapeutic approach was modeled on the body’s immune system, where white blood cells patrol the bloodstream for signs of trouble. The infection fighters can hone in on specific cells in distress, bind to them, and transmit comprehensible signals to self-destruct. The DNA nanorobot emulates this level of specificity using modular components in which different hinges and molecular messages can be switched in and out of the underlying delivery system, much as different engines and tires can be placed on the same chassis, the researchers noted. Because this approach is programmable, the scientists said the system has the potential to treat a variety of diseases.
DNA is a natural biocompatible and biodegradable material, so DNA nanotechnology has been seen as a potential delivery mechanism for drugs and molecular signals, the researchers said. But implementing it has been a challenge, including knowing what type of structure to create, how to program a nanoscale robot, and how to open, close, and reopen that structure to insert, transport, and deliver a payload. The scientists said they have combined several novel elements for the first time to overcome these obstacles. The barrel-shaped structure, for example, has no top or bottom lids, so the payloads can be loaded from the side in a single step without having to open and then reclose it.
In addition, other systems use release mechanisms that respond to DNA or RNA, but the researchers said their mechanism responds to proteins, which are more commonly found on cell surfaces and are largely responsible for transmembrane signaling in cells. They also said this is the first DNA-origami-based system that uses antibody fragments to convey molecular messages so that there is a controlled, programmable way to replicate an immune response or develop new types of targeted therapies.
Source: http://www.masshightech.com/stories/2012/02/13/daily42-Harvard-DNA-nanorobot-may-find-kill-cancer-cells.html
