Active Self‐Assembly of Train‐Shaped DNA Nanostructures via Catalytic Hairpin Assembly Reactions

Abstract

Biomolecular self‐assembly is a powerful approach for fabricating supramolecular architectures. Over the past decade, a myriad of biomolecular assemblies, such as self‐assembly proteins, lipids, and DNA nanostructures, have been used in a wide range of applications, from nano‐optics to nanoelectronics and drug delivery. The method of controlling when and where the self‐assembly starts is essential for assembly dynamics and functionalization. Here, train‐shaped DNA nanostructures are actively self‐assembled using DNA tiles as artificial “carriages,” hairpin structures as “couplers,” and initiators of catalytic hairpin assembly (CHA) reactions as “wrenches.” The initiator wrench can selectively open the hairpin couplers to couple the DNA tile carriages with high product yield. As such, DNA nanotrains are actively prepared with two, three, four, or more carriages. Furthermore, by flexibly modifying the carriages with “biotin seats” (biotin‐modified DNA tiles), streptavidin “passengers” are precisely arranged in corresponding seats. The applications of the CHA‐triggered self‐assembly mechanism are also extended for assembling the large DNA origami dimer. With the creation of 1D architectures established, it is thought that this CHA‐triggered self‐assembly mechanism may provide a new element of control for complex autonomous assemblies from a variety of starting materials with specific sites and times.

Lighting Up CircRNA Using a Linear DNA Nanostructure

“…The CHA-based method has high sensitivity and programmability. However, the occurrence of CHA largely depends on the random diffusion and collision of hairpin probes in solution, suffering from low reaction rate, which compromises the efficiency of signal generation. , What’s more, due to the complex and crowded environment of original biological samples, the amplification efficiency will be further decreased, making the conventional CHA cycle difficult to maintain. Considering the aforementioned issues, we have constructed a linear DNA nanostructure (LDN) in this work, which can be used to directly detect circRNA in complicated samples and even in cells.…”

Prospects and challenges of dynamic DNA nanostructures in biomedical applications

“…One is the synthesis of arbitrary DNA structures, for example, the computer-aided synthesis of large-scale arbitrary two-dimensional and three-dimensional DNA structures proposed by Qian, Dietz, and Yin et al 20 , 40 – 42 The other is the application of various dynamic structures. For example, i-motifs with different conformations under different pH conditions are used to design pH-responsive vectors, 43 – 47 unique DNA sequences are utilized to target specific proteins or DNA sequences and accomplish dynamic structural functions, 36 , 48 , 49 DNA hairpin groups are employed to realize the polymerization chain reaction of specific sequences, 31 , 50 , 51 specially designed three-dimensional nucleic acid structures are used to realize temperature-sensitive drug delivery, 52 , 53 and DNA structures are used in combination with DNA polymerase as the template for rolling circle replication/rolling circle amplification (RCR/RCA) to construct dynamic drug delivery systems. 54 – 56 All the above findings reveal the broad application prospects of dynamic DNA structures in the biomedical field.…”

Disulfide-Containing Molecular Sticker Assists Cellular Delivery of DNA Nanoassemblies by Bypassing Endocytosis

“…The development of DNA nanotechnology leads to the generation of different DNA nanoassemblies with precise programmability, high biocompatibility, and versatile functionality, 1,2 such as DNA origami, 3 DNA hydrogels, 4 and DNA micelles. 5 Furthermore, DNA has been used as a powerful tool to biofunctionalized nanoparticles for morphology control, 6,7 surface modification, 8,9 spatial addressing, 10,11 and dynamic assembly. 12,13 Owing to the unique features of DNA, these DNA hybrid nanoparticles are endowed with targeted function, diversified controllability, and multifunctional properties.…”