A DNA Nanostructure Platform for Directed Assembly of Synthetic Vaccines

Liu, Xiaowei; Xu, Yang; Tao, Yu; Clifford, Craig; Liu, Yan; Yan, Hao; Chang, Yung

doi:10.1021/nl301877k

Cited by 279 publications

(281 citation statements)

References 34 publications

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“…Additionally, such nanostructures can interface with and organize molecules, cells and other materials, 1,12,23−27 thereby enabling biophysical 24,28 and potential biomedical 23,29,30 applications. The self-assembly of individual strands into DNA nanostructures typically involves a thermal gradient in which the system temperature is first raised (e.g., to 80−90°C) and then gradually lowered to room temperature.…”

Section: −22mentioning

confidence: 99%

Isothermal Self-Assembly of Complex DNA Structures under Diverse and Biocompatible Conditions

et al. 2013

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Nucleic acid nanotechnology has enabled researchers to construct a wide range of multidimensional structures in vitro. Until recently, most DNA-based structures were assembled by thermal annealing using high magnesium concentrations and nonphysiological environments. Here, we describe a DNA selfassembly system that can be tuned to form a complex target structure isothermally at any prescribed temperature or homogeneous condition within a wide range. We were able to achieve isothermal assembly between 15 and 69°C in a predictable fashion by altering the strength of strand−strand interactions in several different ways, for example, domain length, GC content, and linker regions between domains. We also observed the assembly of certain structures under biocompatible conditions, that is, at physiological pH, temperature, and salinity in the presence of the molecular crowding agent polyethylene glycol (PEG) mimicking the cellular environment. This represents an important step toward the self-assembly of geometrically precise DNA or RNA structures in vivo. KEYWORDS: DNA nanotechnology, isothermal assembly, single-stranded tiles, biocompatible assembly, molecular crowding N ucleic acid self-assembly has proven to be a powerful tool for constructing nanoscale structures due to the precise and predictable relationship between structure geometry and the encoded sequence. Over the past few decades, a wide range of DNA and RNA-based nanostructures have been demonstrated, including a variety of two-dimensional (2D) and threedimensional (3D) geometries 1−14 and dynamic devices. 15−22Additionally, such nanostructures can interface with and organize molecules, cells and other materials, 1,12,23−27 thereby enabling biophysical 24,28 and potential biomedical 23,29,30 applications. The self-assembly of individual strands into DNA nanostructures typically involves a thermal gradient in which the system temperature is first raised (e.g., to 80−90°C) and then gradually lowered to room temperature. This thermal gradient can be replaced with a chemical gradient of a denaturing agent to isothermally assemble precisely controlled DNA origami structures. 31 In addition to gradient-based assembly, researchers have demonstrated the isothermal formation of extended crystals 12,32,33 using DNA and RNA tiles and discrete structures using DNA origami, 34 both under homogeneous conditions. Isothermal assembly of DNA tiles and origami under homogeneous conditions represents important progress for the assembly of complex DNA nanostructures. Compared with thermal annealing, assembling structures in homogeneous conditions leads to rapid structure formation with higher yield and quality. 34 However, previous work on DNA tile crystals and origami still requires a highly optimized set of assembly conditions (temperature, salinity, etc.) that are structure-dependent and restricted to a narrow range, thereby limiting the scope of potential applications. In contrast, assembly across a wide range of conditions will increase the range of applicatio...

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Section: −22mentioning

confidence: 99%

Isothermal Self-Assembly of Complex DNA Structures under Diverse and Biocompatible Conditions

et al. 2013

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“…Further experiments proved the safety of the DNA carrier because no immune response against the carrier, i.e. a ds DNA tetrahedron, was developed, which could result in tissue damage or trigger autoimmunity [61]. This work shows the great potential of scaffolds generated by DNA nanotechnology to serve as a general platform for vaccine development.…”

Section: Dna Tetrahedramentioning

confidence: 84%

“…6A) [61]. Therefore, streptavidin (STV) was incorporated into the DNA nanocages to form an antigen-adjuvant complex.…”

Section: Dna Tetrahedramentioning

confidence: 99%

Drug delivery systems based on nucleic acid nanostructures

Vries

Zhang

Herrmann

2013

Journal of Controlled Release

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a b s t r a c t a r t i c l e i n f oThe field of DNA nanotechnology has progressed rapidly in recent years and hence a large variety of 1D-, 2D-and 3D DNA nanostructures with various sizes, geometries and shapes is readily accessible. DNA-based nanoobjects are fabricated by straight forward design and self-assembly processes allowing the exact positioning of functional moieties and the integration of other materials. At the same time some of these nanosystems are characterized by a low toxicity profile. As a consequence, the use of these architectures in a biomedical context has been explored. In this review the progress and possibilities of pristine nucleic acid nanostructures and DNA hybrid materials for drug delivery will be discussed. For the latter class of structures, a distinction is made between carriers with an inorganic core composed of gold or silica and amphiphilic DNA block copolymers that exhibit a soft hydrophobic interior.

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“…Yan and Chang et al employed a DNA tetrahedron to assemble an antigen-adjuvant-DNA complex (a synthetic vaccine) and observed strong and long-lasting antibody responses against the model antigen (streptavidin). [82] In-vivo imaging/sensing Ahn et al used a fluorescence-labeled DNA tetrahedron for sentinel lymph nodes imaging. [83] Fan and coworkers built a multi-armed DNA tetrahedron containing a folic acid motif, an NIR emitter (Dylight 755), and a radioactive isotope ( 99m Tc) for tumor-targeting and dual-modality in-vivo imaging.…”

Section: In-vivo Cargo Deliverymentioning

confidence: 99%

Supramolecular Wireframe DNA Polyhedra: Assembly and Applications

Mao

Deng

2017

Chin. J. Chem.

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Wireframe, polyhedral, supramolecular complexes made of DNA have uniform sizes, defined three-dimensional shapes, porous facets, hollow interiors, good biocompatibilities, and chemical functionalizability. They confer great potentials in bottom-up nanoengineering towards various applications. In this review, we summarize recent advances in the rational design and programmed assembly of DNA wireframe polyhedra. Their assembly is based on three distinctively different strategies: individual strands-based assembly, tile-based assembly, and scaffolded DNA origami. Applications of these polyhedral structures in templated nanomaterial assembly and in-vivo cargo delivery are discussed. In the future, expanding the structural complexity and exploring their applications, especially in nanomaterials science and biomedicines, should be a primary focus of this rapidly developing and evolving activity of structural DNA nanotechnology.

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A DNA Nanostructure Platform for Directed Assembly of Synthetic Vaccines

Cited by 279 publications

References 34 publications

Isothermal Self-Assembly of Complex DNA Structures under Diverse and Biocompatible Conditions

Isothermal Self-Assembly of Complex DNA Structures under Diverse and Biocompatible Conditions

Drug delivery systems based on nucleic acid nanostructures

Supramolecular Wireframe DNA Polyhedra: Assembly and Applications

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