DNA Nanostructures that Self-Heal in Serum.

Abstract

Self-assembled DNA nanostructures have potential applications in therapeutics, diagnostics, and synthetic biology. A challenge in using DNA nanostructures in biological environments or cell culture, however, is that they may be degraded by enzymes found in these environments, such as nucleases. Such degradation can be slowed by introducing alternative substrates for nucleases, or by coating nanostructures with membranes or peptides. Here 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. Micrographs of nanotubes show that tiles from solution incorporate into nanotubes and that this incorporation increases nanotube lifetime to several days in serum. We use experimental data to formulate a simple model of nanostructure self-healing. 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 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.