Coating DNA nanostructures and then chemically cross-linking increases resistance to degradation by DNA nuclease enzymes. (Credit: Frances Anastassacos Wyss Institute at Harvard University)

A suite of diverse, multifunctional DNA nanotechnological tools offers unique capabilities and the potential for a broad range of clinical and biomedical research areas. DNA nanostructures have potential to be widely used to transport and present a variety of biologically active molecules such as drugs and immune-enhancing antigens and adjuvants to target cells and tissues in the human body.

In two simple cost-effective steps, the approach first uses a small-molecule, unobtrusive neutralizing agent, PEG-oligolysine, that carries multiple positive charges, to cover DNA origami structures. In contrast to commonly used Mg2+ ions that each neutralize only two negative changes in DNA structures, PEG-oligolysine covers multiple negative charges at one, thus forming a stable electrostatic net, which increases the stability of DNA nanostructures about 400-fold.

Then, by applying a chemical cross-linking reagent known as glutaraldehyde, additional stabilizing bonds are introduced into the electrostatic net, which increases the stability of DNA nanostructures by another 250-fold, extending their half-life into a range that is compatible with a broad range of clinical applications.

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