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In addition, some DNA-based structures have an inherent floppiness that makes three-dimensional shapes collapse. But the building method used to create the barrel–lining up a series of DNA helices into a pleated-sheet structure–seems to provide new strength. “I suspect that Shih’s style of making 3-D structures will prove to be particularly rigid,” says Paul Rothemund, a scientist at the California Institute of Technology in Pasadena, CA who developed the method on which the project is based.

Rothemund adds that one of the most complicated aspects of DNA architecture is confirming that the finished structure takes the shape of the original design. The Harvard students have taken pictures of their DNA barrel using an electron microscope, which shows that it is the right size and shape. They also ran preliminary tests to determine if the barrel can really protect its cargo from the outside environment. Sure enough, they found that a chemical placed inside the barrel is effectively shielded from another chemical that usually binds to it.

If the students can get their creation to work, they’ll overcome one of the lingering problems with DNA-based designs: finding a practical application for the tiny structures. “If … they can make containers for the delivery of drugs, it will demonstrate that using DNA as a technological material really is a useful enterprise!” says Rothemund.

Ultimately, the students hope to create a container that could carry any type of drug and be molecularly targeted to specific types of cells. Newer therapies, such as those that are gene or protein-based, are often difficult to deliver and need to be directed to certain tissues. Some must be delivered via injection or, in a few experimental cases, infused directly into the brain. The students are already working on ways to decorate the barrels with different molecules that bind only to certain cells or proteins.

While the work is still in the very early phase, Shih dreams big about what could happen in the future. “It’s interesting in the long term because we do have so much control over the shapes of these objects,” he says. “People have generated DNA molecules that act as computers, so you could have a drug-delivery device that has an onboard computer that does primitive computations, making decisions about when and where to release the drug.” Of course, Shih says, “there’s still quite a bit of work to be done.”

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Credit: Shawn Douglas and the Harvard iGEM Team

Tagged: Biomedicine

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