FLUORESCENCE IMAGING/CELL BIOLOGY/DRUG DEVELOPMENT: 'DNA origami' technology boosts labeling options for fluorescence microscopy

Fluorescence microscopy is currently limited by the number of colors available, and sometimes the colors blur. But an approach developed at the Wyss Institute for Biologically Inspired Engineering at Harvard University (Cambridge, MA) enables colored dots to be arranged in nearly limitless combinations—thus substantially boosting the number of distinct molecules or cells observable in a sample. And the colors are easily distinguished.

The "DNA origami" technology harnesses the natural ability of DNA to self-assemble. It follows the basic principle that molecular bases in the double helix bind only in specific ways. So a long strand of DNA is programmed to self-assemble by folding in on itself with the help of shorter strands to create predetermined forms.

More than 200 color combinations result from attaching just three colors to a DNA nanotube using DNA origami technology
More than 200 color combinations result from attaching just three colors to a DNA nanotube using "DNA origami" technology. (Image courtesy of the Wyss Institute for Biologically Inspired Engineering, Harvard Medical School)

To these DNA nano-structures, researchers can then attach fluorescent molecules to the desired spots, and thus generate a large pool of labels using just a few basic molecules. "The intrinsic rigidity of the engineered DNA nanostructures is this method's greatest advantage; it holds the fluorescent pattern in place without the use of external forces. It also holds great promise for using the method to study cells in their native environments," says Peng Yin, co-author of a paper describing the work.1 As proof of concept, the team demonstrated that one of their new labels successfully attached to the surface of a yeast cell.

Preliminary work to learn what happens when the fluorescent tags are mixed together in a cell sample has produced promising results. And, according to Yin, it is "low-cost, easy to do, and more robust compared to current methods." The potential for this method includes aiding development of targeted drug-delivery mechanisms and expanding the cellular and molecular activities observable at a disease site.

1. C. Lin et al., Nat. Chem., 4, 832–839, doi:10.1038/nchem.1451(2012).

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