Structural DNA nanotechnology: Immobile Holliday junctions to artificial robots

Author(s):  
Raghu Pradeep Narayanan ◽  
Leeza Abraham

Abstreact: DNA nanotechnology marvels the scientific world with its capabilities to design, engineer, and demonstrate nanoscale shapes. This review is a condensed version walking the reader through the structural developments in the field over the past 40 years starting from the basic design rules of the double-stranded building block to the most recent advancements in self-assembled hierarchically achieved structures to date. It builds off from the fundamental motivation of building 3-dimensional (3D) lattice structures of tunable cavities going all the way up to artificial nanorobots fighting cancer. The review starts by covering the most important developments from the fundamental bottom-up approach of building structures, which is the ‘tile’ based approach covering 1D, 2D, and 3D building blocks, after which, the top-down approach using DNA origami and DNA bricks is also covered. Thereafter, DNA nanostructures assembled using not so commonly used (yet promising) techniques like i-motifs, quadruplexes, and kissing loops are covered. Highlights from the field of dynamic DNA nanostructures have been covered as well, walking the reader through the various approaches used within the field to achieve movement. The article finally concludes by giving the authors a view of what the future of the field might look like while suggesting in parallel new directions that fellow/future DNA nanotechnologists could think about.

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2287
Author(s):  
Martin Glaser ◽  
Sourav Deb ◽  
Florian Seier ◽  
Amay Agrawal ◽  
Tim Liedl ◽  
...  

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.


2020 ◽  
Vol 48 (15) ◽  
pp. 8269-8275 ◽  
Author(s):  
Elisa de Llano ◽  
Haichao Miao ◽  
Yasaman Ahmadi ◽  
Amanda J Wilson ◽  
Morgan Beeby ◽  
...  

Abstract DNA nanotechnology is a rapidly advancing field, which increasingly attracts interest in many different disciplines, such as medicine, biotechnology, physics and biocomputing. The increasing complexity of novel applications requires significant computational support for the design, modelling and analysis of DNA nanostructures. However, current in silico design tools have not been developed in view of these new applications and their requirements. Here, we present Adenita, a novel software tool for the modelling of DNA nanostructures in a user-friendly environment. A data model supporting different DNA nanostructure concepts (multilayer DNA origami, wireframe DNA origami, DNA tiles etc.) has been developed allowing the creation of new and the import of existing DNA nanostructures. In addition, the nanostructures can be modified and analysed on-the-fly using an intuitive toolset. The possibility to combine and re-use existing nanostructures as building blocks for the creation of new superstructures, the integration of alternative molecules (e.g. proteins, aptamers) during the design process, and the export option for oxDNA simulations are outstanding features of Adenita, which spearheads a new generation of DNA nanostructure modelling software. We showcase Adenita by re-using a large nanorod to create a new nanostructure through user interactions that employ different editors to modify the original nanorod.


Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 950
Author(s):  
Jasleen Kaur Daljit Singh ◽  
Minh Tri Luu ◽  
Jonathan F. Berengut ◽  
Ali Abbas ◽  
Shelley F. J. Wickham ◽  
...  

DNA nanotechnology provides methods for building custom membrane-interacting nanostructures with diverse functions, such as shaping membranes, tethering defined numbers of membrane proteins, and transmembrane nanopores. The modification of DNA nanostructures with hydrophobic groups, such as cholesterol, is required to facilitate membrane interactions. However, cholesterol-induced aggregation of DNA origami nanostructures remains a challenge. Aggregation can result in reduced assembly yield, defective structures, and the inhibition of membrane interaction. Here, we quantify the assembly yield of two cholesterol-modified DNA origami nanostructures: a 2D DNA origami tile (DOT) and a 3D DNA origami barrel (DOB), by gel electrophoresis. We found that the DOT assembly yield (relative to the no cholesterol control) could be maximised by reducing the number of cholesterols from 6 to 1 (2 ± 0.2% to 100 ± 2%), optimising the separation between adjacent cholesterols (64 ± 26% to 78 ± 30%), decreasing spacer length (38 ± 20% to 95 ± 5%), and using protective ssDNA 10T overhangs (38 ± 20% to 87 ± 6%). Two-step folding protocols for the DOB, where cholesterol strands are added in a second step, did not improve the yield. Detergent improved the yield of distal cholesterol configurations (26 ± 22% to 92 ± 12%), but samples re-aggregated after detergent removal (74 ± 3%). Finally, we confirmed functional membrane binding of the cholesterol-modified nanostructures. These findings provide fundamental guidelines to reducing the cholesterol-induced aggregation of membrane-interacting 2D and 3D DNA origami nanostructures, improving the yield of well-formed structures to facilitate future applications in nanomedicine and biophysics.


2021 ◽  
Vol 11 (7) ◽  
pp. 2950
Author(s):  
Bolutito Babatunde ◽  
D. Sebastian Arias ◽  
Jonathan Cagan ◽  
Rebecca E. Taylor

Structural DNA nanotechnology involves the design and self-assembly of DNA-based nanostructures. As a field, it has progressed at an exponential rate over recent years. The demand for unique DNA origami nanostructures has driven the development of design tools, but current CAD tools for structural DNA nanotechnology are limited by requiring users to fully conceptualize a design for implementation. This article introduces a novel formal approach for routing the single-stranded scaffold DNA that defines the shape of DNA origami nanostructures. This approach for automated scaffold routing broadens the design space and generates complex multilayer DNA origami designs in an optimally driven way, based on a set of constraints and desired features. This technique computes unique designs of DNA origami assemblies by utilizing shape annealing, which is an integration of shape grammars and the simulated annealing algorithm. The results presented in this article illustrate the potential of the technique to code desired features into DNA nanostructures.


Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1332
Author(s):  
Armando Hernandez-Garcia

Proteins and DNA exhibit key physical chemical properties that make them advantageous for building nanostructures with outstanding features. Both DNA and protein nanotechnology have growth notably and proved to be fertile disciplines. The combination of both types of nanotechnologies is helpful to overcome the individual weaknesses and limitations of each one, paving the way for the continuing diversification of structural nanotechnologies. Recent studies have implemented a synergistic combination of both biomolecules to assemble unique and sophisticate protein–DNA nanostructures. These hybrid nanostructures are highly programmable and display remarkable features that create new opportunities to build on the nanoscale. This review focuses on the strategies deployed to create hybrid protein–DNA nanostructures. Here, we discuss strategies such as polymerization, spatial directing and organizing, coating, and rigidizing or folding DNA into particular shapes or moving parts. The enrichment of structural DNA nanotechnology by incorporating protein nanotechnology has been clearly demonstrated and still shows a large potential to create useful and advanced materials with cell-like properties or dynamic systems. It can be expected that structural protein–DNA nanotechnology will open new avenues in the fabrication of nanoassemblies with unique functional applications and enrich the toolbox of bionanotechnology.


Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1413
Author(s):  
Sofia Ojasalo ◽  
Petteri Piskunen ◽  
Boxuan Shen ◽  
Mauri A. Kostiainen ◽  
Veikko Linko

Viruses are among the most intriguing nanostructures found in nature. Their atomically precise shapes and unique biological properties, especially in protecting and transferring genetic information, have enabled a plethora of biomedical applications. On the other hand, structural DNA nanotechnology has recently emerged as a highly useful tool to create programmable nanoscale structures. They can be extended to user defined devices to exhibit a wide range of static, as well as dynamic functions. In this review, we feature the recent development of virus-DNA hybrid materials. Such structures exhibit the best features of both worlds by combining the biological properties of viruses with the highly controlled assembly properties of DNA. We present how the DNA shapes can act as “structured” genomic material and direct the formation of virus capsid proteins or be encapsulated inside symmetrical capsids. Tobacco mosaic virus-DNA hybrids are discussed as the examples of dynamic systems and directed formation of conjugates. Finally, we highlight virus-mimicking approaches based on lipid- and protein-coated DNA structures that may elicit enhanced stability, immunocompatibility and delivery properties. This development also paves the way for DNA-based vaccines as the programmable nano-objects can be used for controlling immune cell activation.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1502
Author(s):  
Johannes M. Parikka ◽  
Karolina Sokołowska ◽  
Nemanja Markešević ◽  
J. Jussi Toppari

The predictable nature of deoxyribonucleic acid (DNA) interactions enables assembly of DNA into almost any arbitrary shape with programmable features of nanometer precision. The recent progress of DNA nanotechnology has allowed production of an even wider gamut of possible shapes with high-yield and error-free assembly processes. Most of these structures are, however, limited in size to a nanometer scale. To overcome this limitation, a plethora of studies has been carried out to form larger structures using DNA assemblies as building blocks or tiles. Therefore, DNA tiles have become one of the most widely used building blocks for engineering large, intricate structures with nanometer precision. To create even larger assemblies with highly organized patterns, scientists have developed a variety of structural design principles and assembly methods. This review first summarizes currently available DNA tile toolboxes and the basic principles of lattice formation and hierarchical self-assembly using DNA tiles. Special emphasis is given to the forces involved in the assembly process in liquid-liquid and at solid-liquid interfaces, and how to master them to reach the optimum balance between the involved interactions for successful self-assembly. In addition, we focus on the recent approaches that have shown great potential for the controlled immobilization and positioning of DNA nanostructures on different surfaces. The ability to position DNA objects in a controllable manner on technologically relevant surfaces is one step forward towards the integration of DNA-based materials into nanoelectronic and sensor devices.


2019 ◽  
Vol 47 (20) ◽  
pp. 10489-10505 ◽  
Author(s):  
Arun Richard Chandrasekaran ◽  
Jibin Abraham Punnoose ◽  
Lifeng Zhou ◽  
Paromita Dey ◽  
Bijan K Dey ◽  
...  

Abstract MicroRNAs are involved in the crucial processes of development and diseases and have emerged as a new class of biomarkers. The field of DNA nanotechnology has shown great promise in the creation of novel microRNA biosensors that have utility in lab-based biosensing and potential for disease diagnostics. In this Survey and Summary, we explore and review DNA nanotechnology approaches for microRNA detection, surveying the literature for microRNA detection in three main areas of DNA nanostructures: DNA tetrahedra, DNA origami, and DNA devices and motifs. We take a critical look at the reviewed approaches, advantages and disadvantages of these methods in general, and a critical comparison of specific approaches. We conclude with a brief outlook on the future of DNA nanotechnology in biosensing for microRNA and beyond.


2019 ◽  
Vol 48 (1) ◽  
pp. 395-419 ◽  
Author(s):  
Eike-Christian Wamhoff ◽  
James L. Banal ◽  
William P. Bricker ◽  
Tyson R. Shepherd ◽  
Molly F. Parsons ◽  
...  

Structural DNA nanotechnology is beginning to emerge as a widely accessible research tool to mechanistically study diverse biophysical processes. Enabled by scaffolded DNA origami in which a long single strand of DNA is weaved throughout an entire target nucleic acid assembly to ensure its proper folding, assemblies of nearly any geometric shape can now be programmed in a fully automatic manner to interface with biology on the 1–100-nm scale. Here, we review the major design and synthesis principles that have enabled the fabrication of a specific subclass of scaffolded DNA origami objects called wireframe assemblies. These objects offer unprecedented control over the nanoscale organization of biomolecules, including biomolecular copy numbers, presentation on convex or concave geometries, and internal versus external functionalization, in addition to stability in physiological buffer. To highlight the power and versatility of this synthetic structural biology approach to probing molecular and cellular biophysics, we feature its application to three leading areas of investigation: light harvesting and nanoscale energy transport, RNA structural biology, and immune receptor signaling, with an outlook toward unique mechanistic insight that may be gained in these areas in the coming decade.


Nanoscale ◽  
2021 ◽  
Author(s):  
Ying Liu ◽  
Piyumi Wijesekara-Kankanange ◽  
Sriram Kumar ◽  
Weitao Wang ◽  
Xi Ren ◽  
...  

Through targeted binding to the cell membrane, structural DNA nanotechnology has the potential to guide and affix biomolecules such as drugs, growth factors and nanobiosensors to the surfaces of cells....


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