Therapeutic Applications of Programmable DNA Nanostructures

Aye, Seaim Lwin; Sato, Yusuke

doi:10.3390/mi13020315

Cited by 8 publications

(6 citation statements)

References 165 publications

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“…126,127 In addition, the triggered reconfiguration of DNA nanostructures and the control over the optical properties of the systems found extensive applications in intracellular sensing, 128 imaging, 129−131 and therapeutic applications. 132,133 The interaction of light and nucleic acid structures has attracted specific interest. In contrast to the interaction of auxiliary triggers such as pH, chemical agents, enzymes or oligonucleotide fuel/antifuel strands to manipulate DNA structures, all of which alter the composition of the systems by generating waste products, light provides a clean energy source to control the structures and properties of oligonucleotides.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the triggered reconfiguration of nucleic acid strands provides versatile means to guide the formation of DNA nanostructures, to control the aggregation/disaggregation of DNA nanoparticles , or to stimulate the oligomerization of DNA scaffolds such as the switchable dimerization/trimerization of origami tiles , or DNA tetrahedra . Diverse applications of reconfigurable DNA structures were suggested, including the development of sensors, − gated drug carriers for controlled release, − and stimuli-responsive DNA-based materials such as hydrogels revealing controlled stiffness properties, − shape memory, − self-healing, , and mechanical applications. , In addition, the triggered reconfiguration of DNA nanostructures and the control over the optical properties of the systems found extensive applications in intracellular sensing, imaging, − and therapeutic applications. , …”

Section: Introductionmentioning

confidence: 99%

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Photocleavable Ortho-Nitrobenzyl-Protected DNA Architectures and Their Applications

et al. 2023

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This review article introduces mechanistic aspects and applications of photochemically deprotected ortho-nitrobenzyl (ONB)-functionalized nucleic acids and their impact on diverse research fields including DNA nanotechnology and materials chemistry, biological chemistry, and systems chemistry. Specific topics addressed include the synthesis of the ONB-modified nucleic acids, the mechanisms involved in the photochemical deprotection of the ONB units, and the photophysical and chemical means to tune the irradiation wavelength required for the photodeprotection process. Principles to activate ONB-caged nanostructures, ONB-protected DNAzymes and aptamer frameworks are introduced. Specifically, the use of ONB-protected nucleic acids for the phototriggered spatiotemporal amplified sensing and imaging of intracellular mRNAs at the single-cell level are addressed, and control over transcription machineries, protein translation and spatiotemporal silencing of gene expression by ONB-deprotected nucleic acids are demonstrated. In addition, photodeprotection of ONB-modified nucleic acids finds important applications in controlling material properties and functions. These are introduced by the phototriggered fusion of ONB nucleic acid functionalized liposomes as models for cell–cell fusion, the light-stimulated fusion of ONB nucleic acid functionalized drug-loaded liposomes with cells for therapeutic applications, and the photolithographic patterning of ONB nucleic acid-modified interfaces. Particularly, the photolithographic control of the stiffness of membrane-like interfaces for the guided patterned growth of cells is realized. Moreover, ONB-functionalized microcapsules act as light-responsive carriers for the controlled release of drugs, and ONB-modified DNA origami frameworks act as mechanical devices or stimuli-responsive containments for the operation of DNA machineries such as the CRISPR-Cas9 system. The future challenges and potential applications of photoprotected DNA structures are discussed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Photocleavable Ortho-Nitrobenzyl-Protected DNA Architectures and Their Applications

et al. 2023

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“…For gene-editing applications where cleavage precision is paramount, higher fidelity is first required before the photoresponsive I-TevI nuclease can be fully exploited. The modular I-TevI nuclease is however well suited for in vitro purposes and may have applications for controlling the top-down synthesis of DNA nanostructures for 2D and 3D DNA architectures and microarrays and the release of molecular payloads from DNA-based precursors. , As these applications typically do not require high fidelity, the light-responsive I-TevI nuclease developed here could be applied without further engineering for optical control. In summary, we have demonstrated that monomeric homing endonucleases can be reengineered for optical control with programmable specificity by fusion of independent functional domains to LOV domain photoreceptors with notable dynamic range for a first-generation platform.…”

Section: Discussionmentioning

confidence: 99%

A Photoresponsive Homing Endonuclease for Programmed DNA Cleavage

Johnson,

Mart,

Allemann

2023

ACS Synth. Biol.

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Homing endonucleases are used in a wide range of biotechnological applications including gene editing, in gene drive systems, and for the modification of DNA structures, arrays, and prodrugs. However, controlling nuclease activity and sequence specificity remain key challenges when developing new tools. Here a photoresponsive homing endonuclease was engineered for optical control of DNA cleavage by partitioning DNA binding and nuclease domains of the monomeric homing endonuclease I-TevI into independent polypeptide chains. Use of the Aureochrome1a lightoxygen-voltage domain delivered control of dimerization with light. Illumination reduced the concentration needed to achieve 50% cleavage of the homing target site by 6-fold when compared to the dark state, resulting in an up to 9-fold difference in final yields between cleavage products. I-TevI nucleases with and without a native I-TevI zinc finger motif displayed different nuclease activity and sequence preference impacting the promiscuity of the nuclease domain. By harnessing an alternative DNA binding domain, target preference was reprogrammed only when the nuclease lacked the I-TevI zinc finger motif. This work establishes a first-generation photoresponsive platform for spatiotemporal activation of DNA cleavage.

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“…Large negatively charged DNA nanotubes could penetrate into the cell even without conjugation with transfection agents, as the authors suggest, due to the thick shell of DNA chains in the structures. However, it is still unknown how DNA nanotubes are taken up by cells [ 263 ].…”

Section: Delivery Of Dna-based Nanomaterialsmentioning

confidence: 99%

DNA-Based Nanomaterials as Drug Delivery Platforms for Increasing the Effect of Drugs in Tumors

Shishparenok

Furman

Zhdanov

2023

Cancers

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DNA nanotechnology has significantly advanced and might be used in biomedical applications, drug delivery, and cancer treatment during the past few decades. DNA nanomaterials are widely used in biomedical research involving biosensing, bioimaging, and drug delivery since they are remarkably addressable and biocompatible. Gradually, modified nucleic acids have begun to be employed to construct multifunctional DNA nanostructures with a variety of architectural designs. Aptamers are single-stranded nucleic acids (both DNAs and RNAs) capable of self-pairing to acquire secondary structure and of specifically binding with the target. Diagnosis and tumor therapy are prospective fields in which aptamers can be applied. Many DNA nanomaterials with three-dimensional structures have been studied as drug delivery systems for different anticancer medications or gene therapy agents. Different chemical alterations can be employed to construct a wide range of modified DNA nanostructures. Chemically altered DNA-based nanomaterials are useful for drug delivery because of their improved stability and inclusion of functional groups. In this work, the most common oligonucleotide nanomaterials were reviewed as modern drug delivery systems in tumor cells.

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Therapeutic Applications of Programmable DNA Nanostructures

Cited by 8 publications

References 165 publications

Photocleavable Ortho-Nitrobenzyl-Protected DNA Architectures and Their Applications

Photocleavable Ortho-Nitrobenzyl-Protected DNA Architectures and Their Applications

A Photoresponsive Homing Endonuclease for Programmed DNA Cleavage

DNA-Based Nanomaterials as Drug Delivery Platforms for Increasing the Effect of Drugs in Tumors

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