Reconfigurable DNA\nNanocage for Protein Encapsulation\nand Regulation

Creating\nnanomachines capable of precisely capturing,\norganizing,\nand regulating the activity of target biomolecules holds profound\nsignificance for advancing nanotechnology and therapeutics. Here,\nwe develop a multistage reconfigurable DNA nanocage that can enclose\nand modulate proteins through multivalent interactions, activated\nby specific molecular signals. By strategically designing and manipulating\nthe strut architecture of the DNA nanocages, we can achieve precise\ncontrol over their reconfiguration among pyramid, square, and linear\nbranch shapes. Additionally, we demonstrated its ability to capture\nthrombin and effectively inhibit its coagulation activity by incorporating\ntwo thrombin-targeting aptamers into the designed arms of the DNA\nnanocage. The activity of thrombin can be recovered by rearranging\nthe conformation of the DNA nanocage and exposing the protein, thereby\nactivating the coagulation process. This approach enriches the design\ntoolbox for dynamic nanomachines and inspires a new strategy for protein\nencapsulation and regulation with potential future therapeutic applications.