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Biological Chemistry

Delivery Via DNA Nanobots

Nanomedicine: Spring-loaded structures target cancer cells with deadly cargo

by Bethany Halford
February 20, 2012 | A version of this story appeared in Volume 90, Issue 8

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Credit: Campbell Strong, Shawn Douglas & Gaël McGill
Schematic of a DNA nanobot in its closed, hexagonal conformation and sprung open by antigens (green).
Cell-targeting DNA nano-robots bearing antibody-fragment payloads.
Credit: Campbell Strong, Shawn Douglas & Gaël McGill
Schematic of a DNA nanobot in its closed, hexagonal conformation and sprung open by antigens (green).

Just as a postal worker knows to deliver a package to a specified address, a new type of nanoscale robot can deliver therapeutic cargo specifically to cancer cells (Science, DOI: 10.1126/sci​ence.1214081). The nanobot, made from DNA, could be used for targeted drug delivery, taking molecules to the surface of specific cells.

A robot is something that senses and reacts to its environment, explains George M. Church, the Harvard Medical School professor who devised the DNA nanobot along with colleagues Shawn M. Douglas and Ido Bachelet. The Harvard team’s robot is a hexagonal barrel that can carry a variety of payloads and is held together by two “locks” made from DNA aptamers, which are short oligonucleotide strands that can bind antigen targets.

When these locks encounter antigens on the surface of certain cells, the antigens bind each DNA aptamer, springing the locks. The robot opens and delivers its cargo. In one example, the researchers loaded the nanobot with antibodies that signal cancer cells in a tissue culture to shut down. Because of their targeting ability, these nanobots are “considerably smarter than your average therapeutic drug,” Church says.

The researchers built the robot using DNA origami, a technique in which short strands of DNA “staple” one long strand into a predetermined shape. It’s been used previously to make novelty structures, such as boxes and smiley faces. The nanobot is one of the first examples of the technique’s use to build a practical device.

“The report convincingly provides a proof of principle that DNA origami has the capacity to create highly intelligent drugs that only become activated when encountering diseased cells,” comments Jørgen Kjems, a DNA origami expert at the University of Aarhus, in Denmark. “This will inevitably lower the toxicity and thereby the side effects of therapeutic drugs carried by the device. The next step will be to harness DNA nanorobots to withstand the harsh environment of living organisms and prove that they can go all the way to create new and more effective nanomedicines for animals and humans.”

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