DNA Hydrogels with Programmable Condensation, Expansion, and Degradation for Molecular Carriers.

Molecular carriers are necessary for the controlled release of drugs and genes to achieve the desired therapeutic outcomes. DNA hydrogels can be a promising candidate in this application with their distinctive sequence-dependent programmability, which allows precise encapsulation of specific cargo molecules and stimuli-responsive release of them at the target. However, DNA hydrogels are inherently susceptible to the degradation of nucleases, making them vulnerable in a physiological environment. To be an effective molecular carrier, DNA hydrogels should be able to protect encapsulated cargo molecules until they reach the target and release them once they are reached. Here, we develop a simple way of controlling the enzyme resistance of DNA hydrogels for cargo protection and release by using cation-mediated condensation and expansion. We found that DNA hydrogels condensed by spermine are highly resistant to enzymatic degradation. They become degradable again if expanded back to their original, uncondensed state by sodium ions interfering with the interaction between spermine and DNA. These controllable condensation, expansion, and degradation of DNA hydrogels pave the way for the development of DNA hydrogels as an effective molecular carrier.

Harnessing a paper-folding mechanism for reconfigurable DNA origami.

The paper-folding mechanism has been widely adopted in building of reconfigurable macroscale systems because of its unique capabilities and advantages in programming variable shapes and stiffness into a structure1-5. However, it has barely been exploited in the construction of molecular-level systems owing to the lack of a suitable design principle, even though various dynamic structures based on DNA self-assembly6-9 have been developed10-23. Here we propose a method to harness the paper-folding mechanism to create reconfigurable DNA origami structures. The main idea is to build a reference, planar wireframe structure24 whose edges follow a crease pattern in paper folding so that it can be folded into various target shapes. We realized several paper-like folding and unfolding patterns using DNA strand displacement25 with high yield. Orthogonal folding, repeatable folding and unfolding, folding-based microRNA detection and fluorescence signal control were demonstrated. Stimuli-responsive folding and unfolding triggered by pH or light-source change were also possible. Moreover, by employing hierarchical assembly26 we could expand the design space and complexity of the paper-folding mechanism in a highly programmable manner. Because of its high programmability and scalability, we expect that the proposed paper-folding-based reconfiguration method will advance the development of complex molecular systems.