Other post-assembly modification strategies exist, such as the recruitment of cargo to specific sequences or reactive groups introduced into the structure. However, these strategies are not generally applicable as they first require attaching the guest molecule to a specific targeting agent, e.g., aptamers, streptavidin, or zinc finger proteins. Once assembled, functionalized origami suffer from several other limitations that have restricted their widespread use. First, origami are not covalently sealed; rather, they are held together by weak (W-C) hydrogen bonding between the single-stranded DNA scaffold and hundreds of staples. This makes the nanostructures sensitive to thermal denaturation, chaotropic agents, 21 depletion of metal ions, changes in pH, and other treatments. Second, the duplex regions of origami are susceptible to degradation by DNA processing enzymes found in biological media and live cells (e.g., nucleases, RNA polymerase, 25 etc.). In these cases, this can lead to the loss of guest molecules held in place by the relatively short staple oligonucleotides assembled within the structure. Various methods have been developed to improve the stability of duplex regions within DNA origami, such as through the enzymatic or chemical ligation of nick sites located between adjacent staple strands, or the "welding" of strands within or projected from the origami by high-energy ultraviolet light. However, these approaches are not always cost-effective and can compromise the application of introduced functionalities, e.g., due to photobleaching of incorporated fluorophores (D.