Using the DNA origami method, in which complex three-dimensional shapes and objects are constructed by folding strands of DNA, Douglas and Bachelet 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.
“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,” said George Church, Ph.D., a Wyss core faculty member and Professor of Genetics at Harvard Medical School, who is Principal Investigator on the project.