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DNA nanorobot triggers targeted therapeutic responses
Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a robotic 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 research findings appear today in Science.
Using the DNA origami method, in which complex three-dimensional shapes and objects are constructed by folding strands of DNA, Shawn Douglas, Ph.D., a Wyss Technology Development Fellow, and Ido Bachelet, Ph.D., a former Wyss Postdoctoral Fellow who is now an Assistant Professor in the Faculty of Life Sciences and the Nano-Center at Bar-Ilan University in Israel, created a nanosized robot in the form of an open barrel whose two halves are 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 its contents, or payload. The container can hold various types of payloads, including specific molecules with encoded instructions that can interact with specific cell surface signaling receptors.
Douglas and Bachelet used this system to deliver instructions, which were encoded in antibody fragments, to two different types of cancer cells—leukemia and lymphoma. In each case, the message to the cell was to activate its "suicide switch"—a standard feature that allows aging or abnormal cells to be eliminated. And since leukemia and lymphoma cells speak different languages, the messages were written in different antibody combinations.
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 hone in on specific cells in distress, bind to them, and transmit comprehensible signals to them to self-destruct. The DNA nanorobot emulates this level of specificity through the use of 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 programmable power of this type of modularity means the system has the potential to one day be used to treat a variety of diseases.
