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1.
Nat Commun ; 9(1): 535, 2018 02 07.
Article in English | MEDLINE | ID: mdl-29416033

ABSTRACT

Platforms for targeted drug-delivery must simultaneously exhibit serum stability, efficient directed cell internalization, and triggered drug release. Here, using lipid-mediated self-assembly of aptamers, we combine multiple structural motifs into a single nanoconstruct that targets hepatocyte growth factor receptor (cMet). The nanocarrier consists of lipidated versions of a cMet-binding aptamer and a separate lipidated GC-rich DNA hairpin motif loaded with intercalated doxorubicin. Multiple 2',6'-dimethylazobenzene moieties are incorporated into the doxorubicin-binding motif to trigger the release of the chemotherapeutics by photoisomerization. The lipidated DNA scaffolds self-assemble into spherical hybrid-nanoconstructs that specifically bind cMet. The combined features of the nanocarriers increase serum nuclease resistance, favor their import into cells presumably mediated by endocytosis, and allow selective photo-release of the chemotherapeutic into the targeted cells. cMet-expressing H1838 tumor cells specifically internalize drug-loaded nanoconstructs, and subsequent UV exposure enhances cell mortality. This modular approach thus paves the way for novel classes of powerful aptamer-based therapeutics.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Aptamers, Nucleotide/chemistry , Doxorubicin/administration & dosage , Drug Carriers , Nanostructures , Proto-Oncogene Proteins c-met/metabolism , Ultraviolet Rays , Antibiotics, Antineoplastic/chemistry , Azo Compounds/chemistry , Cell Line, Tumor , Doxorubicin/chemistry , Endocytosis , Fluorescence Resonance Energy Transfer , Humans , Lipids/chemistry , Microscopy, Atomic Force
2.
Sci Rep ; 7(1): 7382, 2017 08 07.
Article in English | MEDLINE | ID: mdl-28785065

ABSTRACT

DNA nanostructures represent the confluence of materials science, computer science, biology, and engineering. As functional assemblies, they are capable of performing mechanical and chemical work. In this study, we demonstrate global twisting of DNA nanorails made from two DNA origami six-helix bundles. Twisting was controlled using ethidium bromide or SYBR Green I as model intercalators. Our findings demonstrate that DNA nanorails: (i) twist when subjected to intercalators and the amount of twisting is concentration dependent, and (ii) twisting saturates at elevated concentrations. This study provides insight into how complex DNA structures undergo conformational changes when exposed to intercalators and may be of relevance when exploring how intercalating drugs interact with condensed biological structures such as chromatin and chromosomes, as well as chromatin analogous gene expression devices.


Subject(s)
DNA/chemical synthesis , Intercalating Agents/chemistry , Nanostructures/chemistry , Benzothiazoles , DNA/chemistry , Diamines , Ethidium/chemistry , Models, Molecular , Nucleic Acid Conformation , Organic Chemicals/chemistry , Quinolines
3.
ACS Synth Biol ; 6(10): 1800-1806, 2017 10 20.
Article in English | MEDLINE | ID: mdl-28657718

ABSTRACT

Self-assembled nucleic acids perform biological, chemical, and mechanical work at the nanoscale. DNA-based molecular machines have been designed here to perform work by reacting with cancer-specific miRNA mimics and then regulating gene expression in vitro by tuning RNA polymerase activity. Because RNA production is topologically restrained, the machines demonstrate chromatin analogous gene expression (CAGE). With modular and tunable design features, CAGE has potential for molecular biology, synthetic biology, and personalized medicine applications.


Subject(s)
DNA/genetics , MicroRNAs/genetics , Chromatin/genetics , Gene Expression/genetics , Synthetic Biology/methods
4.
Nanoscale ; 9(29): 10205-10211, 2017 Jul 27.
Article in English | MEDLINE | ID: mdl-28489095

ABSTRACT

Recent results in the assembly of DNA into structures and arrays with nanoscale features and patterns have opened the possibility of using DNA for sub-10 nm lithographic patterning of semiconductor devices. Super-resolution microscopy is being actively developed for DNA-based imaging and is compatible with inline optical metrology techniques for high volume manufacturing. Here, we combine DNA tile assembly with state-dependent super-resolution microscopy to introduce crystal-PAINT as a novel approach for metrology of DNA arrays. Using this approach, we demonstrate optical imaging and characterization of DNA arrays revealing grain boundaries and the temperature dependence of array quality. For finite arrays, analysis of crystal-PAINT images provides further quantitative information of array properties. This metrology approach enables defect detection and classification and facilitates statistical analysis of self-assembled DNA nanostructures.


Subject(s)
DNA/chemistry , Microscopy , Nanostructures/chemistry , Oligonucleotide Array Sequence Analysis , Optical Imaging
5.
Article in English | MEDLINE | ID: mdl-31543931

ABSTRACT

The global demand for digital data is projected to be greater than the supply of semiconductor grade silicon in 2040 [1]. When combined with the need to archive information [2], nucleic acids are being explored as an alternative memory material [1-7]. According to a recent study, the information density of nucleic acid memory (NAM) is 1000 times greater than flash memory and has the ability to last for hundreds of years [1]. Presented here is an algorithm for converting digital data into unique DNA sequences for glacial storage. Biologically inspired, our coding scheme maps hexadecimal characters to sequences of three DNA nucleotides. This mapping avoids repeating sequences and start codons, which could have adverse effects. We were able to encode and decode various file types without error.

7.
Small ; 11(15): 1811-7, 2015 Apr 17.
Article in English | MEDLINE | ID: mdl-25565140

ABSTRACT

Logic gates are devices that can perform logical operations by transforming a set of inputs into a predictable single detectable output. The hybridization properties, structure, and function of nucleic acids can be used to make DNA-based logic gates. These devices are important modules in molecular computing and biosensing. The ideal logic gate system should provide a wide selection of logical operations, and be integrable in multiple copies into more complex structures. Here we show the successful construction of a small DNA-based logic gate complex that produces fluorescent outputs corresponding to the operation of the six Boolean logic gates AND, NAND, OR, NOR, XOR, and XNOR. The logic gate complex is shown to work also when implemented in a three-dimensional DNA origami box structure, where it controlled the position of the lid in a closed or open position. Implementation of multiple microRNA sensitive DNA locks on one DNA origami box structure enabled fuzzy logical operation that allows biosensing of complex molecular signals. Integrating logic gates with DNA origami systems opens a vast avenue to applications in the fields of nanomedicine for diagnostics and therapeutics.


Subject(s)
Computers, Molecular , DNA/chemistry , DNA/ultrastructure , Fuzzy Logic , Signal Processing, Computer-Assisted/instrumentation , Equipment Design , Equipment Failure Analysis
8.
ACS Nano ; 6(11): 10050-3, 2012 Nov 27.
Article in English | MEDLINE | ID: mdl-23030709

ABSTRACT

The DNA origami technique is a recently developed self-assembly method that allows construction of 3D objects at the nanoscale for various applications. In the current study we report the production of a 18 × 18 × 24 nm(3) hollow DNA box origami structure with a switchable lid. The structure was efficiently produced and characterized by atomic force microscopy, transmission electron microscopy, and Förster resonance energy transfer spectroscopy. The DNA box has a unique reclosing mechanism, which enables it to repeatedly open and close in response to a unique set of DNA keys. This DNA device can potentially be used for a broad range of applications such as controlling the function of single molecules, controlled drug delivery, and molecular computing.


Subject(s)
Crystallization/methods , DNA/chemistry , DNA/ultrastructure , Nanostructures/chemistry , Nanostructures/ultrastructure , Macromolecular Substances/chemistry , Materials Testing , Nucleic Acid Conformation , Particle Size , Surface Properties
9.
Int J Mol Sci ; 13(6): 7149-7162, 2012.
Article in English | MEDLINE | ID: mdl-22837684

ABSTRACT

The exploitation of DNA for the production of nanoscale architectures presents a young yet paradigm breaking approach, which addresses many of the barriers to the self-assembly of small molecules into highly-ordered nanostructures via construct addressability. There are two major methods to construct DNA nanostructures, and in the current review we will discuss the principles and some examples of applications of both the tile-based and DNA origami methods. The tile-based approach is an older method that provides a good tool to construct small and simple structures, usually with multiply repeated domains. In contrast, the origami method, at this time, would appear to be more appropriate for the construction of bigger, more sophisticated and exactly defined structures.


Subject(s)
DNA/chemistry , Nanostructures/chemistry , Nanotechnology/methods , Algorithms , Computational Biology , Nucleic Acid Conformation , Software
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