scholarly journals Determinants of ligand-functionalized DNA nanostructure-cell interactions

2021 ◽  
Author(s):  
Glenn A.O. Cremers ◽  
Bas J.H.M. Rosier ◽  
Ab Meijs ◽  
Nicholas B. Tito ◽  
Sander M.J. van Duijnhoven ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Dna Nanotechnology ◽  
Absolute Number ◽  
Design Parameters ◽  
Dna Nanostructures ◽  
Surface Receptors ◽  
Protein Ligands ◽  
Dna Nanostructure ◽  
Functionalized Nanomaterials ◽  
Ligand Orientation

AbstractSynthesis of ligand-functionalized nanomaterials with control over size, shape and ligand orientation, facilitates the design of tailored nanomedicines for therapeutic purposes. DNA nanotechnology has emerged as a powerful tool to rationally construct two- and three-dimensional nanostructures, enabling site-specific incorporation of protein ligands with control over stoichiometry and orientation. To efficiently target cell surface receptors, exploration of the parameters that modulate cellular accessibility of these nanostructures is essential. In this study we systematically investigate tunable design parameters of antibody-functionalized DNA nanostructures binding to therapeutically relevant receptors. We show that, although the native affinity of antibody-functionalized DNA nanostructures remains unaltered, the absolute number of bound surface receptors is lower compared to soluble antibodies and is mainly governed by nanostructure size and DNA handle location. The obtained results provide key insights in the ability of ligand-functionalized DNA nanostructures to bind surface receptors and yields design rules for optimal cellular targeting.

scholarly journals DNA nanostructures coordinate gene silencing in mature plants

2019 ◽  
Vol 116 (15) ◽  
pp. 7543-7548 ◽  
Author(s):  
Huan Zhang ◽  
Gozde S. Demirer ◽  
Honglu Zhang ◽  
Tianzheng Ye ◽  
Natalie S. Goh ◽  
...  
Keyword(s):  
Cell Wall ◽  
Gene Silencing ◽  
Plant Cell ◽  
Mammalian Cells ◽  
Plant Cell Wall ◽  
Plant Cells ◽  
Design Parameters ◽  
Dna Nanostructures ◽  
Dna Nanostructure ◽  
The Impact

Delivery of biomolecules to plants relies onAgrobacteriuminfection or biolistic particle delivery, the former of which is amenable only to DNA delivery. The difficulty in delivering functional biomolecules such as RNA to plant cells is due to the plant cell wall, which is absent in mammalian cells and poses the dominant physical barrier to biomolecule delivery in plants. DNA nanostructure-mediated biomolecule delivery is an effective strategy to deliver cargoes across the lipid bilayer of mammalian cells; however, nanoparticle-mediated delivery without external mechanical aid remains unexplored for biomolecule delivery across the cell wall in plants. Herein, we report a systematic assessment of different DNA nanostructures for their ability to internalize into cells of mature plants, deliver siRNAs, and effectively silence a constitutively expressed gene inNicotiana benthamianaleaves. We show that nanostructure internalization into plant cells and corresponding gene silencing efficiency depends on the DNA nanostructure size, shape, compactness, stiffness, and location of the siRNA attachment locus on the nanostructure. We further confirm that the internalization efficiency of DNA nanostructures correlates with their respective gene silencing efficiencies but that the endogenous gene silencing pathway depends on the siRNA attachment locus. Our work establishes the feasibility of biomolecule delivery to plants with DNA nanostructures and both details the design parameters of importance for plant cell internalization and also assesses the impact of DNA nanostructure geometry for gene silencing mechanisms.

Three-dimensional DNA nanostructures for dual-color microRNA imaging in living cells via hybridization chain reaction

2020 ◽  
Vol 56 (49) ◽  
pp. 6668-6671
Author(s):  
Meng-Mei Lv ◽  
Zhan Wu ◽  
Ru-Qin Yu ◽  
Jian-Hui Jiang
Keyword(s):  
Three Dimensional ◽  
Living Cells ◽  
Fluorescent Imaging ◽  
Hybridization Chain Reaction ◽  
Dna Nanostructures ◽  
Chain Reaction ◽  
Dna Nanostructure ◽  
Dual Color ◽  
Dna Tetrahedron

A well-defined 3D DNA nanostructure was developed by combination of DNA tetrahedron and Y-shaped DNA, which allowed multiplexed, signal amplified fluorescent imaging of miRNAs in living cells via hybridization chain reaction.

DNA nanotechnology-empowered nanoscopic imaging of biomolecules

2021 ◽  
Author(s):  
Fan Li ◽  
Jiang Li ◽  
Baijun Dong ◽  
Fei Wang ◽  
Chunhai Fan ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Dna Nanostructures ◽  
Dna Nanostructure ◽  
Imaging Probes

DNA nanotechnology has led to the rise of DNA nanostructures, which possess programmable shapes and are capable of organizing different functional molecules and materials. A variety of DNA nanostructure-based imaging probes have been developed.

scholarly journals Adenita: interactive 3D modelling and visualization of DNA nanostructures

2020 ◽  
Vol 48 (15) ◽  
pp. 8269-8275 ◽  
Author(s):  
Elisa de Llano ◽  
Haichao Miao ◽  
Yasaman Ahmadi ◽  
Amanda J Wilson ◽  
Morgan Beeby ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Software Tool ◽  
Building Blocks ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
User Interactions ◽  
Dna Nanostructure ◽  
Dna Tiles ◽  
The Creation ◽  
Interactive 3D

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.

scholarly journals Choice of fluorophore affects dynamic DNA nanostructures

2020 ◽  
Author(s):  
Kevin Jahnke ◽  
Helmut Grubmüller ◽  
Maxim Igaev ◽  
Kerstin Göpfrich
Keyword(s):  
Energy Landscape ◽  
Dna Nanotechnology ◽  
Reaction Diffusion ◽  
Md Simulations ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Diffusion Modeling ◽  
Ph Responsive ◽  
Dna Nanostructure ◽  
Potential Impact

The ability to dynamically remodel DNA origami structures or functional nanodevices is highly desired in the field of DNA nanotechnology. Concomitantly, the use of fluorophores to track and validate the dynamics of such DNA-based architectures is commonplace and often unavoidable. It is therefore crucial to be aware of the side effects of popular fluorophores, which are often exchanged without considering the potential impact on the system. Here, we show that the choice of fluorophore can strongly affect the reconfiguration of DNA nanostructures. To this end, we encapsulate a triple-stranded DNA (tsDNA) into water-in-oil compartments and functionalize their periphery with a single-stranded DNA handle (ssDNA). Thus, the tsDNA can bind and unbind from the periphery by reversible opening of the triplex and subsequent strand displacement. Using a combination of experiments, molecular dynamics (MD) simulations, and reaction-diffusion modeling, we demonstrate for twelve different fluorophore combinations that it is possible to alter or even inhibit the DNA nanostructure formation - without changing the DNA sequence. Besides its immediate importance for the design of pH-responsive switches and fluorophore labelling, our work presents a strategy to precisely tune the energy landscape of dynamic DNA nanodevices.

scholarly journals Ultrasound exposure enhances cellular uptake of nanoscale cargos

2021 ◽  
Author(s):  
Kahkashan Bansal ◽  
Anjali Rajwar ◽  
Himanshu Shekhar ◽  
Dhiraj Bhatia
Keyword(s):  
Drug Delivery ◽  
Cellular Uptake ◽  
Propidium Iodide ◽  
Dna Nanotechnology ◽  
Chemotherapeutic Agents ◽  
Dna Nanostructures ◽  
Ultrasound Exposure ◽  
Dna Nanostructure ◽  
Cellular Components ◽  
Further Development

DNA nanotechnology utilizes DNA as a structural molecule to design palette of nanostructures with different shapes and sizes. DNA nanocages have demonstrated significant potential for drug delivery. Therefore, enhancing the delivery of DNA nanocages into cells can improve their efficacy as drug delivery agents. Numerous studies have reported the effects of ultrasound for enhancing drug delivery across biological barriers. The mechanical bioeffects caused by cell-ultrasound interaction can cause sonoporation, leading to enhanced uptake of drugs, nanoparticles, and chemotherapeutic agents through membranes. Whether ultrasound exposure can enhance the delivery of DNA nanocages has not been explored, which is the focus of this study. Specifically, we investigated the effects of ultrasound on the cellular uptake of propidium Iodide, fluorescent dextrans, and DNA nanostructures). We provide evidence of modulation of pore formation in the cell membrane by ultrasound by studying the intracellular uptake of the impermeable dye, propidium iodide. Treatment of cells with low amplitudes of ultrasound enhanced the uptake of different sizes of dextrans and DNA based nanodevices. These findings could serve as the foundation for further development ultrasound-enabled DNA nanostructure delivery and for specific understanding of underlying biological mechanisms of interaction between ultrasound parameters and cellular components; the knowledge that can be further explored for potential biological and biomedical applications.

scholarly journals In vivo cloning of artificial DNA nanostructures

2008 ◽  
Vol 105 (46) ◽  
pp. 17626-17631 ◽  
Author(s):  
Chenxiang Lin ◽  
Sherri Rinker ◽  
Xing Wang ◽  
Yan Liu ◽  
Nadrian C. Seeman ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Dna Nanostructures ◽  
Scientific Enterprise ◽  
Dna Nanostructure ◽  
Copy Numbers ◽  
Artificial Dna ◽  
Difficult Challenge ◽  
Endonuclease Vii

Mimicking nature is both a key goal and a difficult challenge for the scientific enterprise. DNA, well known as the genetic-information carrier in nature, can be replicated efficiently in living cells. Today, despite the dramatic evolution of DNA nanotechnology, a versatile method that replicates artificial DNA nanostructures with complex secondary structures remains an appealing target. Previous success in replicating DNA nanostructures enzymatically in vitro suggests that a possible solution could be cloning these nanostructures by using viruses. Here, we report a system where a single-stranded DNA nanostructure (Holliday junction or paranemic cross-over DNA) is inserted into a phagemid, transformed into XL1-Blue cells and amplified in vivo in the presence of helper phages. High copy numbers of cloned nanostructures can be obtained readily by using standard molecular biology techniques. Correct replication is verified by a number of assays including nondenaturing PAGE, Ferguson analysis, endonuclease VII digestion, and hydroxyl radical autofootprinting. The simplicity, efficiency, and fidelity of nature are fully reflected in this system. UV-induced psoralen cross-linking is used to probe the secondary structure of the inserted junction in infected cells. Our data suggest the possible formation of the immobile four-arm junction in vivo.

scholarly journals DNA Nanostructures Coordinate Gene Silencing in Mature Plants

2019 ◽  
Author(s):  
Huan Zhang ◽  
Gozde S. Demirer ◽  
Honglu Zhang ◽  
Tianzheng Ye ◽  
Natalie S. Goh ◽  
...  
Keyword(s):  
Cell Wall ◽  
Gene Silencing ◽  
Plant Cell ◽  
Mammalian Cells ◽  
Plant Cell Wall ◽  
Plant Cells ◽  
Design Parameters ◽  
Dna Nanostructures ◽  
Dna Nanostructure ◽  
The Impact

AbstractPlant bioengineering may generate high yielding and stress-resistant crops amidst a changing climate and a growing global population (1–3). However, delivery of biomolecules to plants relies onAgrobacteriuminfection (4) or biolistic particle delivery (5), the former of which is only amenable to DNA delivery. The difficulty in delivering functional biomolecules such as RNA to plant cells is due to the plant cell wall which is absent in mammalian cells and poses the dominant physical barrier to exogenous biomolecule delivery in plants. DNA nanostructure-mediated biomolecule delivery is an effective strategy to deliver cargoes across the lipid bilayer of mammalian cells, however, nanoparticle-mediated delivery remains unexplored for passive biomolecule delivery across the cell wall in plants. Herein, we report a systematic assessment of different DNA nanostructures for their ability to internalize into cells of mature plants, deliver small interfering RNAs (siRNAs), and effectively silence a constitutively-expressed gene inNicotiana benthamianaleaves. We show that nanostructure internalization into plant cells and the corresponding gene silencing efficiency depends on the DNA nanostructure size, shape, compactness, stiffness, and location of the siRNA attachment locus on the nanostructure. We further confirm that the internalization efficiency of DNA nanostructures correlates with their respective gene silencing efficiencies, but that the endogenous gene silencing pathway depends on the siRNA attachment locus. Our work establishes the feasibility of biomolecule delivery to plants with DNA nanostructures, and details both the design parameters of importance for plant cell internalization, and also assesses the impact of DNA nanostructure geometry for gene silencing mechanisms.

Chemical ligation of an entire DNA Origami nanostructure

Nanoscale ◽  
2021 ◽  
Author(s):  
Nicole Weizenmann ◽  
Gerda Scheidgen-Kleyboldt ◽  
Jingjing Ye ◽  
Cordula Bärbel Krause ◽  
Dominik Kauert ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Dna Nanotechnology ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Chemical Ligation

Within the field of DNA nanotechnology, numerous methods were developed to produce complex two- and three-dimensional DNA nanostructures for many different emerging applications. These structures typically suffer from a low...

scholarly journals Membrane activity of a DNA-based ion channel depends on the stability of its double-stranded structure.

2021 ◽  
Author(s):  
Diana Morzy ◽  
Himanshu Joshi ◽  
Sarah E Sandler ◽  
Aleksei Aksimentiev ◽  
Ulrich F Keyser
Keyword(s):  
Ion Channels ◽  
Lipid Bilayer ◽  
Lipid Membranes ◽  
Degrees Of Freedom ◽  
Dna Nanotechnology ◽  
Md Simulations ◽  
Dna Nanostructures ◽  
Base Pairs ◽  
Dna Nanostructure ◽  
Synthetic Ion Channels

Structural DNA nanotechnology has emerged as a promising method for designing spontaneously-inserting and fully-controllable synthetic ion channels. However, both insertion efficiency and stability of existing DNA-based ion channels leave much room for improvement. Here, we demonstrate an approach to overcoming the unfavorable DNA-lipid interactions that hinder the formation of a stable transmembrane pore. Our all-atom MD simulations and experiments show that the insertion-driving cholesterol modifications, when introduced at an end of a DNA strand, are likely to cause fraying of the terminal base pairs as the DNA nanostructure adopts its energy-minimum configuration in the membrane. We also find that fraying of base pairs distorts nicked DNA constructs when embedded in a lipid bilayer. Here, we show that DNA nanostructures that do not have discontinuities (nicks) in their DNA backbones form considerably more stable DNA-induced conductive pores and insert into lipid membranes with a higher efficiency than the equivalent nicked constructs. Moreover, lack of nicks allows to design and maintain membrane-spanning helices in a tilted orientation within lipid bilayer. Thus, reducing the conformational degrees of freedom of the DNA nanostructures enables better control over their function as synthetic ion channels.

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