We've seen various experimental approaches that aim to increase the efficacy of chemotherapy while also reducing its damaging side effects by specifically targeting cancer cells. The latest encouraging development comes from Harvard's Wyss Institute for Biologically Inspired Engineering where researchers have created a barrel-like robotic device made from DNA that could carry molecular instructions into specific cells and tell them to self-destruct. Because the DNA-based device could be programmed to target a variety of cells, it could be used to treat a range of diseases in addition to providing hope in the fight against cancer.
The team based their programmable nanotherapeutic approach on the body's own immune system in which white blood cells circulate in the blood ready to attack an infection where it has developed. Just like white blood cells that are able to hone in on specific cells in distress and bind to them, the researchers created a DNA barrel that can recognize and seek out combinations of cell-surface proteins, including disease markers.
By folding strands of DNA in what is known as the "DNA origami" method, the researchers create a three-dimensional open barrel shape whose two halves are connected by a hinge. The container is held shut by special DNA latches that reconfigure when they find their specific target - cancer cells, for example - causing the two halves to swing open and expose the container's payload. These payloads can be of various types, including molecules with encoded instructions that can interact with surface signaling receptors.
Shawn Douglas, Ph.D., and Ido Bachelet, Ph.D., used the DNA barrel to deliver instructions encoded in antibody fragments to two different types of cancer cells - leukemia and lymphoma. Since leukemia and lymphoma speak different languages the messages were written in different antibody combinations. But the message was the same - activate the cell's so called "suicide gene," which will cause a cell to kill itself through apoptosis.
It is the researchers' modular approach, which allows different hinges and different message payloads to be switched and swapped, that gives the system the potential to treat a variety of diseases.
Although DNA nanotechnology has been widely recognized for its potential as a delivery mechanism for drugs and molecular signals because of its natural biocompatibility and biodegradability, there have been significant hurdles concerning its implementation - 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 the device.
The Wyss researchers overcame the first two problems by creating a barrel-shaped structure with no top or bottom lids. This allows the payloads to be loaded from the side while the structure is closed instead of having to first open the structure, insert the payload, and then re-close it. Meanwhile, for the programming problem they developed a mechanism that responds to proteins. While other systems use release mechanisms that respond to DNA or RNA, proteins are more commonly found on cell surfaces and are largely responsible for transmembrane signaling in cells.
The researchers say theirs is the first DNA-origami-based system that that uses antibody fragments to convey molecular messages, offering a controlled and programmable way to replicate an immune system response or develop new types of targeted therapies.
The team's research findings appear in the journal Science and the creators discuss their DNA nanorobot in the video below.
Source: Wyss Institute
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