Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers

Haque, Farzin; Shu, Dan; Shu, Yi; Shlyakhtenko, Luda S.; Rychahou, Piotr G.; Evers, B. Mark; Guo, Peixuan

doi:10.1016/j.nantod.2012.06.010

Cited by 179 publications

(282 citation statements)

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“…Nanoscaffolds assembled from tectonic unit monomers can be readily ornamented with at least as many independent functional units as the number of tectonic units from which they are composed (see Functionalization and Modification). The functional units could be multiple copies of the same compound for increased potency, a collection of different therapeutic agents in a manner similar to cocktail therapy, signal or regulatory elements, or any combination of the above, dependent only on the objectives of the designer [106,107]. This combination of specific, programmable supramolecular structures with diverse functional units in a single, entirely RNA compound, allows precise positioning of different functional modules in three-dimensional space.…”

Section: Rna Architectonic Approach (Tectorna)mentioning

confidence: 99%

“…This combination of specific, programmable supramolecular structures with diverse functional units in a single, entirely RNA compound, allows precise positioning of different functional modules in three-dimensional space. This, for example, can provide an avenue to address the vital problems of stability, targeting, and multivalency in nanomedicine [95,102,103,107], and can form the basis of preprogrammed arrays [43], mediate the growth and distribution of other NPs [94,108], or form patterned scaffolds for tissue engineering or other applications [47].…”

Section: Rna Architectonic Approach (Tectorna)mentioning

confidence: 99%

“…It has greatly enhanced simplicity and biocompatibility when compared with peptide, liposomal, or synthetic nanomaterial conjugation for RNA-based functionalities; RNA nanoparticles can be equipped with custom tailored combinations of therapeutic agents or biosensors, which show promise to improve targeting and penetration of cells or tissues safely and efficiently [76,95,107], provide "cocktail"-like multi-target therapies [106], advanced imaging or imaging concurrent with therapeutics [110]. In addition, they can do so while guaranteeing strict control of the 3D orientation and stoichiometry of those agents [102,104].…”

Section: Rna Architectonic Approach (Tectorna)mentioning

confidence: 99%

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Engineered RNA Nanodesigns for Applications in RNA Nanotechnology

Afonin¹,

Lindsay²,

Shapiro³

2013

DNA and RNA Nanotechnology

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IntroductionThe physical world presents a very different landscape at the nanometer scale. Physical phenomena such as inertia and gravity vanish from view; instead the interactions of matter and energy are dominated by other phenomena like wave-particle duality, uncertainty, and quantum electrodynamics. Nanotechnology is the engineering of functional systems at this scale, where the axioms that govern material and device design differ dramatically from those found at the macroscale level. More precisely, "nanotechnology" typically encompasses both the miniaturization of existing technologies to the nanoscale, and the discipline of engineering molecular-scale systems from the bottom up, producing constructs with fundamentally new qualities that revolutionize human engineering, from materials and manufacturing, electronics, and information technology, to medicine, biotechnology, energy, and even security. The array of goals and applications in nanotechnology intersects with an equally wide array of techniques and materials with their own emergent properties in the field. One such branch is concerned with the re-engineering of biological mechanisms, systems, and molecules in new forms with new utilities, broadly termed bio-nanotechnology.The field of nanotechnology taking advantage of nucleic acids has its origins in the work of Nadrian Seeman and coworkers who have, over the past 30 years, spearheaded the development of DNA nano-object fabrication utilizing DNA self-assembly [1][2][3][4][5][6]. Briefly, DNA nanotechnology uses the nature of DNA complementarity for the construction of DNA tiles with discrete secondary structure by canonical WatsonCrick interactions (G-C and A-T base pairing), using a relatively small number of structural rules fundamentally based on Holliday junction motifs. The use of these rules has resulted in the engineering and characterization of numerous DNA 3D nanoscaffolds with different connectiviities [7][8][9][10][11][12][13][14][15][16][17][18] and the ability for some of them to promote targeted delivery by functioning as DNA nano-capsules [19][20][21] or DNA nano-carriers for other functionialities [22]. Another powerful technique called DNA "origami", developed by Paul Rothemund [23], has been extended from its original scope for designing different 2D DNA shapes [24] and functional templates [25][26][27][28] Abstract Nucleic acids have emerged as an extremely promising platform for nanotechnological applications because of their unique biochemical properties and functions. RNA, in particular, is characterized by relatively high thermal stability, diverse structural flexibility, and its capacity to perform a variety of functions in nature. These properties make RNA a valuable platform for bio-nanotechnology, specifically RNA Nanotechnology, that can create de novo nanostructures with unique functionalities through the design, integration, and re-engineering of powerful mechanisms based on a variety of existing RNA structures and their fundamental biochemical properties. This review...

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Section: Rna Architectonic Approach (Tectorna)mentioning

confidence: 99%

Section: Rna Architectonic Approach (Tectorna)mentioning

confidence: 99%

Section: Rna Architectonic Approach (Tectorna)mentioning

confidence: 99%

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Engineered RNA Nanodesigns for Applications in RNA Nanotechnology

Afonin¹,

Lindsay²,

Shapiro³

2013

DNA and RNA Nanotechnology

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“…In this report, we focus our attention to recently introduced concepts of interdependent, cognate nucleic acid nanoparticles assembly that take advantage of dynamic interactions and consequent shape-switching to trigger the activation of multiple functionalities. Particularly, we discuss re-association of thermodynamically driven complementary nanocubes ("cube" and complementary "anti-cube") into functional duplexes that do not require toehold interactions or extensive computational design, bringing a new perspective for utility of nucleic acid nanoparticles as a drug carriers, biosensors, and templates for the formation of siRNA duplexes.Keywords: RNA/DNA nanoparticles, Nucleic Acid re-association, Complementary nanoparticles Nucleic acids occupy a unique role in nanotechnology as materials which offer both biocompatibility and high versatility in design, allowing for fine-tunable and dynamic responses from a diverse library of possible structural motifs which can serve both as scaffolds and active agents [1][2][3][4][5] . To optimize the activity of nucleic acid nanoparticles, approaches to assembling dynamic RNA and RNA-DNA hybrid nanostructures have traditionally relied upon computer-assisted design and the use of single-stranded (ss) DNA or RNA toeholds for the resultant activation of switches or strand exchange [6][7][8][9][10] .…”

mentioning

confidence: 99%

“…Keywords: RNA/DNA nanoparticles, Nucleic Acid re-association, Complementary nanoparticles Nucleic acids occupy a unique role in nanotechnology as materials which offer both biocompatibility and high versatility in design, allowing for fine-tunable and dynamic responses from a diverse library of possible structural motifs which can serve both as scaffolds and active agents [1][2][3][4][5] . To optimize the activity of nucleic acid nanoparticles, approaches to assembling dynamic RNA and RNA-DNA hybrid nanostructures have traditionally relied upon computer-assisted design and the use of single-stranded (ss) DNA or RNA toeholds for the resultant activation of switches or strand exchange [6][7][8][9][10] .…”

mentioning

confidence: 99%

Activation of Multiple Functionalities Through Interacting Nanoparticles

Chandler¹,

Halman²,

Khisamutdinov³

2017

DNA and RNA Nanotechnology

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dynamic interactions and consequent shape-switching to trigger the activation of multiple functionalities 11 . As a proof of concept, our work extensively characterized nanoparticle cube assemblies consisting of six nucleic acid strands with varying numbers of DNA or RNA strands in their composition. The re-association of complementary nanocubes-designated "cube" and "anti-cube"-into duplexes was thermodynamically driven and thus did not require toehold interactions or extensive computational design ( Figure 1).Variation in DNA/RNA ratios within the nanocube constructs allows for expanded flexibility in fine-tuning properties such as thermostability, immunogenicity, and the rates at which cognate nanocubes re-associate to form duplexes. While previously studied nucleic acid-based therapeutics have shown some promise in overcoming toxicity, immunostimulation continues to inhibit their transition into clinical settings 12 . The immune response to nanocubes of varying compositions was measured via the activation and secretion of type I interferon (INFα) and various pro-inflammatory cytokines and chemokines established as common biomarkers 13 . Results of this test panel indicated that RNA nanocubes may serve as vaccine adjuvants while DNA nanocubes could be used as potential drug delivery agents.The re-association of complementary DNA nanoparticles was used to co-transcriptionally trigger the formation of RNA nanoparticles by supplementing all six DNA strands of the cubes with split T7 RNA polymerase promoters. In addition, the re-association of complementary DNA nanoparticles was shown to trigger the activation of embedded split RNA aptamers, as visualized using the synthetic RNA aptamer Broccoli 14 . Upon re-association of the complimentary "Broc" and "Coli" cubes, the completed aptamer bound to the fluorophore DFHBI-1T to mimic the fluorescence of green fluorescent protein (GFP). Furthermore, the re-association of complementary nanoparticles was shown to trigger the activation of energy transfer and RNA interference in cells. Sets of cognate cubes functionalized with split Dicer Substrate (DS) RNAs against either BCL2 and PLK1, targets Abstract: Nucleic acids are biocompatible, robust, and highly versatile polymers that can be used to design fine-tunable and dynamically responsive nanostructures. In this report, we focus our attention to recently introduced concepts of interdependent, cognate nucleic acid nanoparticles assembly that take advantage of dynamic interactions and consequent shape-switching to trigger the activation of multiple functionalities. Particularly, we discuss re-association of thermodynamically driven complementary nanocubes ("cube" and complementary "anti-cube") into functional duplexes that do not require toehold interactions or extensive computational design, bringing a new perspective for utility of nucleic acid nanoparticles as a drug carriers, biosensors, and templates for the formation of siRNA duplexes.Keywords: RNA/DNA nanoparticles, Nucleic Acid re-association, Complementary nanopa...

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