'DNA robot' makes cancer self-destruct

Posted by Kate Taylor

Harvard researchers have created a tiny  'DNA robot' that can seek out and destroy specific cells - including cancer cells.

Using the DNA origami method, in which complex three-dimensional shapes and objects are built by folding strands of DNA, the Wyss Institute for Biologically Inspired Engineering team created a nanosized robot in the form of an open barrel whose two halves are connected by a hinge.

This barrel's 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 change shape; the barrel then opens and delivers its contents.

The team's successfully used the system to deliver instructions,  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.

The approach is similar to the body's own immune system, in which white blood cells home in on specific cells in distress, bind to them, and transmit signals to them to self-destruct. The DNA nanorobot is just as specific, as different hinges and molecular messages can be switched in and out. This means it could potentially be used to treat a variety of diseases.

While similar techniques have been tried before, there are several new elements to the Harvard method.

Because the barrel-shaped structure has no top or bottom lids, the payloads can be loaded from the side in a single step - without having to open the structure first and then reclose it.

Also, while other systems use release mechanisms that respond to DNA or RNA, this one responds to proteins, which are more commonly found on cell surfaces and are largely responsible for transmembrane signaling in cells.

Finally, this is the first DNA-origami-based system that uses antibody fragments to convey molecular messages - offering a controlled and programmable way to replicate an immune response or develop new types of targeted therapies.

"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," says principal investigator George Church.