Prospects and challenges of dynamic DNA nanostructures in biomedical applications

Abstract

The physicochemical nature of DNA allows the assembly of highly predictable structures via several fabrication strategies, which have been applied to make breakthroughs in various fields. Moreover, DNA nanostructures are regarded as materials with excellent editability and biocompatibility for biomedical applications. The ongoing maintenance and release of new DNA structure design tools ease the work and make large and arbitrary DNA structures feasible for different applications. However, the nature of DNA nanostructures endows them with several stimulus-responsive mechanisms capable of responding to biomolecules, such as nucleic acids and proteins, as well as biophysical environmental parameters, such as temperature and pH. Via these mechanisms, stimulus-responsive dynamic DNA nanostructures have been applied in several biomedical settings, including basic research, active drug delivery, biosensor development, and tissue engineering. These applications have shown the versatility of dynamic DNA nanostructures, with unignorable merits that exceed those of their traditional counterparts, such as polymers and metal particles. However, there are stability, yield, exogenous DNA, and ethical considerations regarding their clinical translation. In this review, we first introduce the recent efforts and discoveries in DNA nanotechnology, highlighting the uses of dynamic DNA nanostructures in biomedical applications. Then, several dynamic DNA nanostructures are presented, and their typical biomedical applications, including their use as DNA aptamers, ion concentration/pH-sensitive DNA molecules, DNA nanostructures capable of strand displacement reactions, and protein-based dynamic DNA nanostructures, are discussed. Finally, the challenges regarding the biomedical applications of dynamic DNA nanostructures are discussed.

D-Mannose prevents bone loss under weightlessness

“…Other measures are also used to treat bone loss [60][61][62]. However, these methods are mainly aimed at promoting bone formation and have little effect on inhibiting osteoclast resorption.…”

Dendrimer-like Hierarchical Framework Nucleic Acid for Real-Time Imaging of Intracellular Trafficking

“…Recently, the hierarchical assembly of multiple basic DNA building units into DNA nanostructures with a larger size and higher complexity has become appealing due to its high yield and relatively low cost. − Obviously, these high hierarchical DNA structures provide more active sites for multiple modifications and can achieve versatile cellular functionality. The assembly of multiple FNA monomers results in a high valency for the attachment of molecules ranging from nucleic acids to proteins.…”

Modulation of Enzyme Cascade Activity by Local Substrate Enrichment and Exclusion on DNA Nanostructures

“…DNA self-assembly has revolutionized the understanding and organization of biomacromolecules on the nanoscale. Beginning with Ned Seeman’s construction of the artificial “Holliday” junction, in the past four decades, DNA self-assembly has been widely adopted for the design and fabrication of prescribed and sophisticated 1D, 2D, and 3D nanostructures. − Several breakthroughs in the methodology of DNA self-assembly, such as DNA crossovers, scaffolded DNA origami, and DNA bricks, have empowered the design capability toward more complex structures and functionality , as well as folding nanostructures with single-stranded nucleic acids . Because of unique features of programmable and prescribed geometry, sequence-addressable assembly, and adaption to various bioconjugations, DNA nanostructures hold great promise to organize complex molecular systems with precise control of spatial arrangements. , For example, multienzyme systems were assembled on DNA nanostructures for controlling interenzyme distances, − engineering biomimetic swinging arms, − and confining enzymes within nanocages. − DNA nanostructures can also be used to engineer micro-/nanoenvironment for modulating biochemical activities, such as the stabilized hydration layer and decreased local pH .…”

“…Beginning with Ned Seeman's construction of the artificial "Holliday" junction, in the past four decades, DNA selfassembly has been widely adopted for the design and fabrication of prescribed and sophisticated 1D, 2D, and 3D nanostructures. 11−13 Several breakthroughs in the method-ology of DNA self-assembly, such as DNA crossovers, 14 scaffolded DNA origami, 15 and DNA bricks, 16 have empowered the design capability toward more complex structures and functionality 17,18 as well as folding nanostructures with singlestranded nucleic acids. 19 Because of unique features of programmable and prescribed geometry, sequence-addressable assembly, and adaption to various bioconjugations, 20 DNA nanostructures hold great promise to organize complex molecular systems with precise control of spatial arrangements.…”