Researchers from the University of Rome Tor Vergata and the University of Montreal have reported the design and synthesis of a nanoscale molecular slingshot made of DNA that could potentially shoot and target drugs to specific regions of the human body.
The slingshot is made of a synthetic DNA strand that can be loaded with drugs and act as the rubber band of a slingshot. The 2 ends of the “rubber band” have anchors that stick to a target antibody. When the anchors are triggered by the target antibody, the rubber band stretches and the loaded drug is released.
“One impressive feature about this molecular slingshot is that it can only be triggered by the specific antibody recognizing the anchoring tags of the DNA ‘rubber band’,” Francesco Ricci, associate professor of chemistry at the University of Rome Tor Vergata, said in prepared remarks. “By simply changing these tags, one can thus program the slingshot to release a drug in response to a variety of specific antibodies. Since different antibodies are markers of different diseases, this could become a very specific weapon in the clinician’s hands.”
“Another great property of our slingshot is its high versatility,” Alexis Vallée-Bélisle, assistant professor in the department of chemistry at the University of Montreal, added. “For example, until now we have demonstrated the working principle of the slingshot using 3 different trigger antibodies, including an HIV antibody, and employing nucleic acids as model drugs. But thanks to the high programmability of DNA chemistry, one can now design the DNA slingshot to ‘shoot’ a wide range of threrapeutic molecules.”
“Designing this molecular slingshot was a great challenge,” principal author Simona Ranallo said. “It required a long series of experiments to find the optimal design, which keeps the drug loaded in ‘rubber band’ in the absence of the antibody, without affecting too much its shooting efficiency once the antibody triggers the slingshot.”
The team plans to identify a specific disease and drug to test its slingshot in cells and then in mice.
“We envision that similar molecular slingshots may be used in the near future to deliver drugs to specific locations in the body. This would drastically improve the efficiency of drugs as well as decrease their toxic secondary effects,” Ricci said.
