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Article: Force-free activation of Notch with DNA origami.

Kim, Hyun Min / Bathe, Mark

2024 Volume 40, Issue 4, Page(s) 293–295

Abstract: The Notch signaling pathway is a highly conserved, fundamental process to embryogenesis and neurogenesis. While force-induced conformational change is known to activate Notch receptors, Smyrlaki et al. recently used DNA origami to reveal an additional, ... ...

Abstract	The Notch signaling pathway is a highly conserved, fundamental process to embryogenesis and neurogenesis. While force-induced conformational change is known to activate Notch receptors, Smyrlaki et al. recently used DNA origami to reveal an additional, force-independent mode of Notch activation via soluble presentation of spatially controlled ligand nanopatterns.
MeSH term(s)	Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Signal Transduction ; Embryonic Development ; Neurogenesis ; DNA/genetics
Chemical Substances	Receptors, Notch ; DNA (9007-49-2)
Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2024.03.001
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Article ; Online: Scalable Nucleic Acid Storage and Retrieval Using Barcoded Microcapsules.

Banal, James L / Bathe, Mark

ACS applied materials & interfaces

2021 Volume 13, Issue 42, Page(s) 49729–49736

Abstract: Rapid advances in nucleic acid sequencing and synthesis technologies have spurred a major need to collect, store, and sequence the DNA and RNA from viral, bacterial, and mammalian sources and organisms. However, current approaches to storing nucleic ... ...

Abstract	Rapid advances in nucleic acid sequencing and synthesis technologies have spurred a major need to collect, store, and sequence the DNA and RNA from viral, bacterial, and mammalian sources and organisms. However, current approaches to storing nucleic acids rely on a low-temperature environment and require robotics for access, posing challenges for scalable and low-cost nucleic acid storage. Here, we present an alternative method for storing nucleic acids, termed Preservation and Access of Nucleic aciDs using barcOded micRocApsules (PANDORA). Nucleic acids spanning kilobases to gigabases and from different sources, including animals, bacteria, and viruses, are encapsulated into silica microcapsules to protect them from environmental denaturants at room temperature. Molecular barcodes attached to each microcapsule enable sample pooling and subsequent identification and retrieval using fluorescence-activated sorting. We demonstrate quantitative storage and rapid access to targeted nucleic acids from a pool emulating standard retrieval operations implemented in conventional storage systems, including recovery of 100,000-200,000 samples and Boolean logic selection using four unique barcodes. Quantitative polymerase chain reaction and short-read sequencing of the retrieved samples validated the sorting experiments and the integrity of the released nucleic acids. Our proposed approach offers a scalable long-term, room-temperature storage and retrieval of nucleic acids with high sample fidelity.
MeSH term(s)	Animals ; Capsules ; DNA/chemistry ; DNA/genetics ; Fluorescence ; Humans ; Materials Testing ; Polymerase Chain Reaction ; RNA/chemistry ; RNA/genetics ; Temperature
Chemical Substances	Capsules ; RNA (63231-63-0) ; DNA (9007-49-2)
Language	English
Publishing date	2021-10-15
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.1c14985
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Functionalizing DNA origami to investigate and interact with biological systems.

Knappe, Grant A / Wamhoff, Eike-Christian / Bathe, Mark

Nature reviews. Materials

2022 Volume 8, Issue 2, Page(s) 123–138

Abstract: DNA origami has emerged as a powerful method to generate DNA nanostructures with dynamic properties and nanoscale control. These nanostructures enable complex biophysical studies and the fabrication of next-generation therapeutic devices. For these ... ...

Abstract	DNA origami has emerged as a powerful method to generate DNA nanostructures with dynamic properties and nanoscale control. These nanostructures enable complex biophysical studies and the fabrication of next-generation therapeutic devices. For these applications, DNA origami typically needs to be functionalized with bioactive ligands and biomacromolecular cargos. Here, we review methods developed to functionalize, purify, and characterize DNA origami nanostructures. We identify remaining challenges, such as limitations in functionalization efficiency and characterization. We then discuss where researchers can contribute to further advance the fabrication of functionalized DNA origami.
Language	English
Publishing date	2022-12-19
Publishing country	England
Document type	Journal Article
ISSN	2058-8437
ISSN	2058-8437
DOI	10.1038/s41578-022-00517-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Engineering Exciton Dynamics with Synthetic DNA Scaffolds.

Hart, Stephanie M / Gorman, Jeffrey / Bathe, Mark / Schlau-Cohen, Gabriela S

Accounts of chemical research

2023 Volume 56, Issue 15, Page(s) 2051–2061

Abstract: Excitons are the molecular-scale currency of electronic energy. Control over excitons enables energy to be directed and harnessed for light harvesting, electronics, and sensing. Excitonic circuits achieve such control by arranging electronically active ... ...

Abstract	Excitons are the molecular-scale currency of electronic energy. Control over excitons enables energy to be directed and harnessed for light harvesting, electronics, and sensing. Excitonic circuits achieve such control by arranging electronically active molecules to prescribe desired spatiotemporal dynamics. Photosynthetic solar energy conversion is a canonical example of the power of excitonic circuits, where chromophores are positioned in a protein scaffold to perform efficient light capture, energy transport, and charge separation. Synthetic systems that aim to emulate this functionality include self-assembled aggregates, molecular crystals, and chromophore-modified proteins. While the potential of this approach is clear, these systems lack the structural precision to control excitons or even test the limits of their power. In recent years, DNA origami has emerged as a designer material that exploits biological building blocks to construct nanoscale architectures. The structural precision afforded by DNA origami has enabled the pursuit of naturally inspired organizational principles in a highly precise and scalable manner. In this Account, we describe recent developments in DNA-based platforms that spatially organize chromophores to construct tunable excitonic systems. The high fidelity of DNA base pairing enables the formation of programmable nanoscale architectures, and sequence-specific placement allows for the precise positioning of chromophores within the DNA structure. The integration of a wide range of chromophores across the visible spectrum introduces spectral tunability. These excitonic DNA-chromophore assemblies not only serve as model systems for light harvesting, solar conversion, and sensing but also lay the groundwork for the integration of coupled chromophores into larger-scale nucleic acid architectures.We have used this approach to generate DNA-chromophore assemblies of strongly coupled delocalized excited states through both sequence-specific self-assembly and the covalent attachment of chromophores. These strategies have been leveraged to independently control excitonic coupling and system-bath interaction, which together control energy transfer. We then extended this framework to identify how scaffold configurations can steer the formation of symmetry-breaking charge transfer states, paving the way toward the design of dual light-harvesting and charge separation DNA machinery. In an orthogonal application, we used the programmability of DNA chromophore assemblies to change the optical emission properties of strongly coupled dimers, generating a series of fluorophore-modified constructs with separable emission properties for fluorescence assays. Upcoming advances in the chemical modification of nucleotides, design of large-scale DNA origami, and predictive computational methods will aid in constructing excitonic assemblies for optical and computing applications. Collectively, the development of DNA-chromophore assemblies as a platform for excitonic circuitry offers a pathway to identifying and applying design principles for light harvesting and molecular electronics.
MeSH term(s)	Photosynthesis ; Energy Transfer ; Fluorescent Dyes ; DNA/chemistry
Chemical Substances	Fluorescent Dyes ; DNA (9007-49-2)
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1483291-4
ISSN	1520-4898 ; 0001-4842
ISSN (online)	1520-4898
ISSN	0001-4842
DOI	10.1021/acs.accounts.3c00086
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Article ; Online: Programming 2D Supramolecular Assemblies with Wireframe DNA Origami.

Wang, Xiao / Jun, Hyungmin / Bathe, Mark

Journal of the American Chemical Society

2022 Volume 144, Issue 10, Page(s) 4403–4409

Abstract: Wireframe DNA origami offers the ability to program nearly arbitrary 2D and 3D nanoscale geometries, with six-helix bundle (6HB) edge designs providing both geometric versatility and fidelity with respect to the target origami shape. Because individual ... ...

Abstract	Wireframe DNA origami offers the ability to program nearly arbitrary 2D and 3D nanoscale geometries, with six-helix bundle (6HB) edge designs providing both geometric versatility and fidelity with respect to the target origami shape. Because individual DNA origami objects are limited in size by the length of the DNA scaffold, here, we introduce a hierarchical self-assembly strategy to overcome this limitation by programming supramolecular assemblies and periodic arrays using wireframe DNA origami objects as building blocks. Parallel half-crossovers are used together with lateral cohesive interactions between staples and the scaffold to introduce symmetry into supramolecular assemblies constructed from single DNA origami units that cannot be self-assembled directly using base-stacking or conventional antiparallel crossover designs. This hierarchical design approach can be applied readily to 2D wireframe DNA origami designed using the top-down sequence design strategy METIS without any prerequisites on scaffold and staple routing. We demonstrate the utility of our strategy by fabricating dimers and self-limiting hexameric superstructures using both triangular and hexagonal wireframe origami building blocks. We generalize our self-assembly approach to fabricate close-packed and non-close-packed periodic 2D arrays. Visualization using atomic force microscopy and transmission electron microscopy demonstrates that superstructures exhibit similar structural integrity to that of the individual origami building blocks designed using METIS. Our results offer a general platform for the design and fabrication of 2D materials for a variety of applications.
MeSH term(s)	DNA/chemistry ; Microscopy, Atomic Force ; Nanostructures/chemistry ; Nanotechnology/methods ; Nucleic Acid Conformation
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2022-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.1c11332
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Article: Isometric Hamming embeddings of weighted graphs.

Berleant, Joseph / Sheridan, Kristin / Condon, Anne / Williams, Virginia Vassilevska / Bathe, Mark

Discrete applied mathematics (Amsterdam, Netherlands : 1988)

2023 Volume 332, Page(s) 119–128

Abstract: ... A ... ...

Abstract	A mapping
Language	English
Publishing date	2023-02-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1467965-6
ISSN	0166-218X
ISSN	0166-218X
DOI	10.1016/j.dam.2023.02.005
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Article ; Online: Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors.

Dobrovolskaia, Marina A / Bathe, Mark

Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology

2020 Volume 13, Issue 1, Page(s) e1657

Abstract: Gene therapeutics including siRNAs, anti-sense oligos, messenger RNAs, and CRISPR ribonucleoprotein complexes offer unmet potential to treat over 7,000 known genetic diseases, as well as cancer, through targeted in vivo modulation of aberrant gene ... ...

Abstract	Gene therapeutics including siRNAs, anti-sense oligos, messenger RNAs, and CRISPR ribonucleoprotein complexes offer unmet potential to treat over 7,000 known genetic diseases, as well as cancer, through targeted in vivo modulation of aberrant gene expression and immune cell activation. Compared with viral vectors, nonviral delivery vectors offer controlled immunogenicity and low manufacturing cost, yet suffer from limitations in toxicity, targeting, and transduction efficiency. Structured DNA assemblies fabricated using the principle of scaffolded DNA origami offer a new nonviral delivery vector with intrinsic, yet controllable immunostimulatory properties and virus-like spatial presentation of ligands and immunogens for cell-specific targeting, activation, and control over intracellular trafficking, in addition to low manufacturing cost. However, the relative utilities and limitations of these vectors must clearly be demonstrated in preclinical studies for their clinical potential to be realized. Here, we review the major capabilities, opportunities, and challenges we foresee in translating these next-generation delivery and vaccine vectors to the clinic. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
MeSH term(s)	DNA ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; Vaccines
Chemical Substances	Vaccines ; DNA (9007-49-2)
Language	English
Publishing date	2020-07-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2502698-7
ISSN	1939-0041 ; 1939-5116
ISSN (online)	1939-0041
ISSN	1939-5116
DOI	10.1002/wnan.1657
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Article: Factorization and pseudofactorization of weighted graphs.

Sheridan, Kristin / Berleant, Joseph / Bathe, Mark / Condon, Anne / Williams, Virginia Vassilevska

Discrete applied mathematics (Amsterdam, Netherlands : 1988)

2023 Volume 337, Page(s) 81–105

Abstract: For unweighted graphs, finding isometric embeddings of a ... ...

Abstract	For unweighted graphs, finding isometric embeddings of a graph
Language	English
Publishing date	2023-05-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1467965-6
ISSN	0166-218X
ISSN	0166-218X
DOI	10.1016/j.dam.2023.04.019
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Article ; Online: Ultrafast dense DNA functionalization of quantum dots and rods for scalable 2D array fabrication with nanoscale precision.

Chen, Chi / Luo, Xin / Kaplan, Alexander E K / Bawendi, Moungi G / Macfarlane, Robert J / Bathe, Mark

Science advances

2023 Volume 9, Issue 32, Page(s) eadh8508

Abstract: Scalable fabrication of two-dimensional (2D) arrays of quantum dots (QDs) and quantum rods (QRs) with nanoscale precision is required for numerous device applications. However, self-assembly-based fabrication of such arrays using DNA origami typically ... ...

Abstract	Scalable fabrication of two-dimensional (2D) arrays of quantum dots (QDs) and quantum rods (QRs) with nanoscale precision is required for numerous device applications. However, self-assembly-based fabrication of such arrays using DNA origami typically suffers from low yield due to inefficient QD and QR DNA functionalization. In addition, it is challenging to organize solution-assembled DNA origami arrays on 2D device substrates while maintaining their structural fidelity. Here, we reduced manufacturing time from a few days to a few minutes by preparing high-density DNA-conjugated QDs/QRs from organic solution using a dehydration and rehydration process. We used a surface-assisted large-scale assembly (SALSA) method to construct 2D origami lattices directly on solid substrates to template QD and QR 2D arrays with orientational control, with overall loading yields exceeding 90%. Our fabrication approach enables the scalable, high fidelity manufacturing of 2D addressable QDs and QRs with nanoscale orientational and spacing control for functional 2D photonic devices.
MeSH term(s)	Quantum Dots/chemistry ; DNA/chemistry ; Oligonucleotide Array Sequence Analysis
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2023-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adh8508
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Article: Scalable Nucleic Acid Storage and Retrieval Using Barcoded Microcapsules

Banal, James L. / Bathe, Mark

ACS applied materials & interfaces. 2021 Oct. 15, v. 13, no. 42

2021

Abstract	Rapid advances in nucleic acid sequencing and synthesis technologies have spurred a major need to collect, store, and sequence the DNA and RNA from viral, bacterial, and mammalian sources and organisms. However, current approaches to storing nucleic acids rely on a low-temperature environment and require robotics for access, posing challenges for scalable and low-cost nucleic acid storage. Here, we present an alternative method for storing nucleic acids, termed Preservation and Access of Nucleic aciDs using barcOded micRocApsules (PANDORA). Nucleic acids spanning kilobases to gigabases and from different sources, including animals, bacteria, and viruses, are encapsulated into silica microcapsules to protect them from environmental denaturants at room temperature. Molecular barcodes attached to each microcapsule enable sample pooling and subsequent identification and retrieval using fluorescence-activated sorting. We demonstrate quantitative storage and rapid access to targeted nucleic acids from a pool emulating standard retrieval operations implemented in conventional storage systems, including recovery of 100,000–200,000 samples and Boolean logic selection using four unique barcodes. Quantitative polymerase chain reaction and short-read sequencing of the retrieved samples validated the sorting experiments and the integrity of the released nucleic acids. Our proposed approach offers a scalable long-term, room-temperature storage and retrieval of nucleic acids with high sample fidelity.
Keywords	DNA ; RNA ; ambient temperature ; barcoding ; genetic barcoding ; mammals ; quantitative polymerase chain reaction ; silica
Language	English
Dates of publication	2021-1015
Size	p. 49729-49736.
Publishing place	American Chemical Society
Document type	Article
ISSN	1944-8252
DOI	10.1021/acsami.1c14985
Database	NAL-Catalogue (AGRICOLA)

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