Many of us often refer to our bodies as harmonious temples. However, at the molecular level, daily events are anything but Zen, as cellular environments are often damaging to biological materials, especially those added exogenously—a challenge bioengineers have faced for some time when designing DNA nanostructures. Yet now, investigators from Johns Hopkins University have developed new DNA nanostructures that can heal themselves in serum. Findings from the new study were released today in Nano Letters through an article titled, “DNA Nanostructures that Self-Heal in Serum.”
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine. However, these intriguing structures don’t persist long in biological environments because of enzymes called nucleases that degrade DNA. Someday, doctors could introduce DNA nanostructures to the human body to diagnose diseases or deliver medications, among other applications. But first, they must find a way to protect or repair the molecules when nucleases attack.
Previously, researchers developed several approaches to stabilize the structures in serum, such as chemically modifying or coating the DNA. However, making this stabilized DNA can be expensive and time-consuming, and the modifications could affect the nanostructures’ biocompatibility or function. In the current study, the researchers wanted to develop a self-repair process that could substantially extend the lifetime of DNA nanostructures.
The researchers designed DNA nanotubes that self-assemble from smaller DNA “tiles.” In serum at body temperature, the nanostructures degraded within only 24 hours. However, when the researchers added extra tiles to serum containing the nanotubes, the building blocks repaired damaged structures, extending their lifetimes to more than 96 hours.
“We demonstrate a means by which degradation can be reversed in situ through the repair of nanostructure defects. To demonstrate this effect, we show that degradation rates of DNA nanotubes, micron-scale self-assembled structures, are at least 4-fold lower in the presence of tiles that can repair nanotube defects during the degradation process,” the authors write. “Micrographs of nanotubes show that tiles from solution incorporate into nanotubes and that this incorporation increases nanotube lifetime to several days in serum.”
By labeling the original nanotubes and the extra tiles with differently colored fluorescent dyes, the team determined that the additional small DNA pieces repaired the degrading structures both by replacing damaged tiles and by joining to the nanotube ends. The researchers developed a computer model of the process that indicated DNA nanostructures could be maintained for months or longer using the self-healing method.
“This model suggests how introducing even a relatively low rate of repair could allow a nanostructure to survive almost indefinitely because of a dynamic equilibrium between microscale repair and degradation processes,” the authors conclude. “The ability to repair nanostructures could thus allow particular structures or devices to operate for long periods of time and might offer a single means to resist different types of chemical degradation.”