Concept and Development of Framework Nucleic Acids.

The blooming field of structural DNA nanotechnology harnessing the material properties of nucleic acids has attracted widespread interest. The exploitation of the precise and programmable Watson-Crick base pairing of DNA or RNA has led to the development of exquisite nucleic acid nanostructures from one to three dimensions. The advances of computer-aided tools facilitate automated design of DNA nanostructures with various sizes and shapes. Especially, the construction of shell or skeleton DNA frameworks, or more recently dubbed "framework nucleic acids" (FNAs) provides a means to organize molecules or nanoparticles with nanometer precision. The intrinsic biological properties and tailorable functionalities of FNAs hold great promise for physical, chemical, and biological applications. This Perspective highlights state-of-the-art design and construction, of precisely assembled FNAs, and outlines the challenges and opportunities for exploiting the structural potential of FNAs for translational applications.

[1]  Hao Yan,et al.  Programming molecular topologies from single-stranded nucleic acids , 2018, Nature Communications.

[2]  H. Pei,et al.  Electrochemical single nucleotide polymorphisms genotyping on surface immobilized three-dimensional branched DNA nanostructure , 2011 .

[3]  Hao Yan,et al.  Complex wireframe DNA origami nanostructures with multi-arm junction vertices. , 2015, Nature nanotechnology.

[4]  A. Serganov,et al.  Preparation and Crystallization of Riboswitches. , 2016, Methods in molecular biology.

[5]  Shawn M. Douglas,et al.  Multilayer DNA origami packed on a square lattice. , 2009, Journal of the American Chemical Society.

[6]  Stephen Neidle,et al.  Crystal structure of parallel quadruplexes from human telomeric DNA , 2002, Nature.

[7]  Hao Yan,et al.  DNA directed self-assembly of anisotropic plasmonic nanostructures. , 2011, Journal of the American Chemical Society.

[8]  Peixuan Guo The emerging field of RNA nanotechnology. , 2010, Nature nanotechnology.

[9]  J. Reif,et al.  DNA-Templated Self-Assembly of Protein Arrays and Highly Conductive Nanowires , 2003, Science.

[10]  Ehud Gazit,et al.  Self-assembled peptide nanostructures: the design of molecular building blocks and their technological utilization. , 2007, Chemical Society reviews.

[11]  J. Chao,et al.  Folding super-sized DNA origami with scaffold strands from long-range PCR. , 2012, Chemical communications.

[12]  Hao Yan,et al.  Challenges and opportunities for structural DNA nanotechnology. , 2011, Nature nanotechnology.

[13]  Adam T Woolley,et al.  Polymerase chain reaction based scaffold preparation for the production of thin, branched DNA origami nanostructures of arbitrary sizes. , 2009, Nano letters.

[14]  R. Symons,et al.  Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites , 1987, Cell.

[15]  Chunhai Fan,et al.  A DNA-Origami chip platform for label-free SNP genotyping using toehold-mediated strand displacement. , 2010, Small.

[16]  Xiaolei Zuo,et al.  Ultrasensitive electrochemical detection of prostate-specific antigen by using antibodies anchored on a DNA nanostructural scaffold. , 2014, Analytical chemistry.

[17]  Hao Yan,et al.  Charge transport within a three-dimensional DNA nanostructure framework. , 2012, Journal of the American Chemical Society.

[18]  Johannes B. Woehrstein,et al.  Multiplexed 3D Cellular Super-Resolution Imaging with DNA-PAINT and Exchange-PAINT , 2014, Nature Methods.

[19]  Hao Yan,et al.  DNA-origami-directed self-assembly of discrete silver-nanoparticle architectures. , 2010, Angewandte Chemie.

[20]  Shawn M. Douglas,et al.  A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads , 2012, Science.

[21]  Jie Chao,et al.  Dynamic Patterning Programmed by DNA Tiles Captured on a DNA Origami Substrate , 2009, Nature nanotechnology.

[22]  Hao Yan,et al.  Low temperature assembly of functional 3D DNA-PNA-protein complexes. , 2014, Journal of the American Chemical Society.

[23]  Chunhai Fan,et al.  DNA nanostructure-decorated surfaces for enhanced aptamer-target binding and electrochemical cocaine sensors. , 2011, Analytical chemistry.

[24]  Stefan A. Maier,et al.  High-resolution mapping of electron-beam-excited plasmon modes in lithographically defined gold nanostructures. , 2011, Nano letters.

[25]  Chunhai Fan,et al.  Regenerable electrochemical immunological sensing at DNA nanostructure-decorated gold surfaces. , 2011, Chemical communications.

[26]  Hao Yan,et al.  Gold nanoparticle self-similar chain structure organized by DNA origami. , 2010, Journal of the American Chemical Society.

[27]  C. Fan,et al.  Ultrasensitive IgG quantification using DNA nano-pyramids , 2014 .

[28]  Lulu Qian,et al.  Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns , 2017, Nature.

[29]  Hao Yan,et al.  Complex silica composite nanomaterials templated with DNA origami , 2018, Nature.

[30]  Andrew J Turberfield,et al.  Single-molecule protein encapsulation in a rigid DNA cage. , 2006, Angewandte Chemie.

[31]  Hao Yan,et al.  Single-stranded DNA and RNA origami , 2017, Science.

[32]  J. Chao,et al.  A Surface‐Confined Proton‐Driven DNA Pump Using a Dynamic 3D DNA Scaffold , 2016, Advanced materials.

[33]  N. Seeman,et al.  Designed Two-Dimensional DNA Holliday Junction Arrays Visualized by Atomic Force Microscopy , 1999 .

[34]  Jing Wang,et al.  Self-assembly of size-controlled liposomes on DNA nanotemplates , 2016, Nature chemistry.

[35]  Chunhai Fan,et al.  A DNA-based system for selecting and displaying the combined result of two input variables , 2015, Nature Communications.

[36]  Russell P. Goodman,et al.  High-resolution structural analysis of a DNA nanostructure by cryoEM. , 2009, Nano letters.

[37]  Hao Yan,et al.  Self-Assembled Water-Soluble Nucleic Acid Probe Tiles for Label-Free RNA Hybridization Assays , 2008, Science.

[38]  A. Phan,et al.  The solution structure and internal motions of a fragment of the cytidine-rich strand of the human telomere. , 2000, Journal of molecular biology.

[39]  Faisal A. Aldaye,et al.  Loading and selective release of cargo in DNA nanotubes with longitudinal variation. , 2010, Nature chemistry.

[40]  Matthew J. A. Wood,et al.  DNA cage delivery to mammalian cells. , 2011, ACS nano.

[41]  L. Forró,et al.  Cellular toxicity of carbon-based nanomaterials. , 2006, Nano letters.

[42]  Carlos E. Castro,et al.  Engineering Cell Surface Function with DNA Origami , 2017, Advanced materials.

[43]  A. Khademhosseini,et al.  DNA directed self-assembly of shape-controlled hydrogels , 2013, Nature Communications.

[44]  T. G. Martin,et al.  Synthetic Lipid Membrane Channels Formed by Designed DNA Nanostructures , 2012, Science.

[45]  Jonathan Bath,et al.  A DNA-based molecular motor that can navigate a network of tracks. , 2012, Nature nanotechnology.

[46]  Shawn M. Douglas,et al.  Folding DNA into Twisted and Curved Nanoscale Shapes , 2009, Science.

[47]  Jie Chao,et al.  Single-step rapid assembly of DNA origami nanostructures for addressable nanoscale bioreactors. , 2013, Journal of the American Chemical Society.

[48]  Nadrian C Seeman,et al.  At the crossroads of chemistry, biology, and materials: structural DNA nanotechnology. , 2003, Chemistry & biology.

[49]  Sandhya P Koushika,et al.  A synthetic icosahedral DNA-based host-cargo complex for functional in vivo imaging. , 2011, Nature communications.

[50]  P. Yin,et al.  Complex shapes self-assembled from single-stranded DNA tiles , 2012, Nature.

[51]  Daniel G. Anderson,et al.  Molecularly Self-Assembled Nucleic Acid Nanoparticles for Targeted In Vivo siRNA Delivery , 2012, Nature nanotechnology.

[52]  Xiaobing Zhang,et al.  mRNA-Initiated, Three-Dimensional DNA Amplifier Able to Function inside Living Cells. , 2018, Journal of the American Chemical Society.

[53]  Raluca Tiron,et al.  DNA Origami Mask for Sub-Ten-Nanometer Lithography. , 2016, ACS nano.

[54]  Jie Chao,et al.  Multivalent capture and detection of cancer cells with DNA nanostructured biosensors and multibranched hybridization chain reaction amplification. , 2014, Analytical chemistry.

[55]  N. Seeman,et al.  Synthesis from DNA of a molecule with the connectivity of a cube , 1991, Nature.

[56]  Shawn M. Douglas,et al.  Self-assembly of DNA into nanoscale three-dimensional shapes , 2009, Nature.

[57]  Hendrik Dietz,et al.  Efficient Production of Single-Stranded Phage DNA as Scaffolds for DNA Origami , 2015, Nano letters.

[58]  N. Seeman,et al.  DNA double-crossover molecules. , 1993, Biochemistry.

[59]  N. Seeman,et al.  Construction of a DNA-Truncated Octahedron , 1994 .

[60]  Cody W. Geary,et al.  A single-stranded architecture for cotranscriptional folding of RNA nanostructures , 2014, Science.

[61]  Casey Grun,et al.  Programmable self-assembly of three-dimensional nanostructures from 104 unique components , 2017, Nature.

[62]  S. Howorka,et al.  Changing of the guard , 2016, Science.

[63]  Hao Yan,et al.  Interenzyme substrate diffusion for an enzyme cascade organized on spatially addressable DNA nanostructures. , 2012, Journal of the American Chemical Society.

[64]  Dan Zhu,et al.  Self-assembled DNA tetrahedral optofluidic lasers with precise and tunable gain control. , 2013, Lab on a chip.

[65]  N. Seeman Nanomaterials based on DNA. , 2010, Annual review of biochemistry.

[66]  Jie Chao,et al.  Solving mazes with single-molecule DNA navigators , 2018, Nature Materials.

[67]  Hao Yan,et al.  Functional DNA nanotube arrays: bottom-up meets top-down. , 2007, Angewandte Chemie.

[68]  Russell P. Goodman,et al.  Rapid Chiral Assembly of Rigid DNA Building Blocks for Molecular Nanofabrication , 2005, Science.

[69]  Hao Yan,et al.  A DNA Nanostructure‐based Biomolecular Probe Carrier Platform for Electrochemical Biosensing , 2010, Advanced materials.

[70]  L. Jaeger,et al.  The architectonics of programmable RNA and DNA nanostructures. , 2006, Current opinion in structural biology.

[71]  C. Mao,et al.  DNA nanotechnology. , 2004, BioTechniques.

[72]  Juwen Shen,et al.  Dynamic Modulation of DNA Hybridization Using Allosteric DNA Tetrahedral Nanostructures. , 2016, Analytical chemistry.

[73]  Nadrian C. Seeman,et al.  An Overview of Structural DNA Nanotechnology , 2007, Molecular biotechnology.

[74]  Hendrik Dietz,et al.  Biotechnological mass production of DNA origami , 2017, Nature.

[75]  N. Seeman,et al.  An immobile nucleic acid junction constructed from oligonucleotides , 1983, Nature.

[76]  Hao Yan,et al.  Directional Regulation of Enzyme Pathways through the Control of Substrate Channeling on a DNA Origami Scaffold. , 2016, Angewandte Chemie.

[77]  Peng Yin,et al.  Casting inorganic structures with DNA molds , 2014, Science.

[78]  M. I. Setyawati,et al.  Electrochemical Quantification of Escherichia coli with DNA Nanostructure , 2015 .

[79]  Hao Yan,et al.  DNA Origami with Complex Curvatures in Three-Dimensional Space , 2011, Science.

[80]  A. Serganov,et al.  A Decade of Riboswitches , 2013, Cell.

[81]  C. Mao,et al.  Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra , 2008, Nature.

[82]  W. Chiu,et al.  Designer nanoscale DNA assemblies programmed from the top down , 2016, Science.

[83]  Juwen Shen,et al.  Valency-Controlled Framework Nucleic Acid Signal Amplifiers. , 2018, Angewandte Chemie.

[84]  W. Gilbert,et al.  Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis , 1988, Nature.

[85]  Petra Schwille,et al.  Amphipathic DNA origami nanoparticles to scaffold and deform lipid membrane vesicles. , 2015, Angewandte Chemie.

[86]  J. Reif,et al.  Construction, analysis, ligation, and self-assembly of DNA triple crossover complexes , 2000 .

[87]  M. Dinger,et al.  I-motif DNA structures are formed in the nuclei of human cells , 2018, Nature Chemistry.

[88]  Hao Yan,et al.  In vivo cloning of artificial DNA nanostructures , 2008, Proceedings of the National Academy of Sciences.

[89]  Hao Yan,et al.  DNA-cholesterol barges as programmable membrane-exploring agents. , 2014, ACS nano.

[90]  Hao Yan,et al.  Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion , 2016, Nature Communications.

[91]  Hao Yan,et al.  Site-specific synthesis and in situ immobilization of fluorescent silver nanoclusters on DNA nanoscaffolds by use of the Tollens reaction. , 2011, Angewandte Chemie.

[92]  Chenxiang Lin,et al.  Knitting Complex Weaves with Dna Origami This Review Comes from a Themed Issue on Nucleic Acids Edited Dna and the Biosynthetic Advantage Single-layer Dna Origami Multi-layer Dna Origami Scaling to Greater Complexity Conclusions and Future Outlook , 2022 .

[93]  Wei Sun,et al.  Nanoscale growth and patterning of inorganic oxides using DNA nanostructure templates. , 2013, Journal of the American Chemical Society.

[94]  Chunhai Fan,et al.  DNA Nanotechnology-Enabled Interfacial Engineering for Biosensor Development. , 2018, Annual review of analytical chemistry.

[95]  Nadrian C. Seeman,et al.  DNA Components for Molecular Architecture , 1997 .

[96]  Richard A. Muscat,et al.  DNA nanotechnology from the test tube to the cell. , 2015, Nature nanotechnology.

[97]  Vivek V. Thacker,et al.  Lipid-Bilayer-Spanning DNA Nanopores with a Bifunctional Porphyrin Anchor , 2013, Angewandte Chemie.

[98]  N. Seeman,et al.  Design and self-assembly of two-dimensional DNA crystals , 1998, Nature.

[99]  Samara L. Reck-Peterson,et al.  Tug-of-War in Motor Protein Ensembles Revealed with a Programmable DNA Origami Scaffold , 2012, Science.

[100]  Weihong Tan,et al.  Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics , 2013, Proceedings of the National Academy of Sciences.

[101]  J. Reif,et al.  Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[102]  Baoquan Ding,et al.  A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo , 2018, Nature Biotechnology.

[103]  Oleg Gang,et al.  Self-organized architectures from assorted DNA-framed nanoparticles. , 2016, Nature chemistry.

[104]  Xiaolei Zuo,et al.  Biomacromolecular nanostructures-based interfacial engineering: from precise assembly to precision biosensing , 2018 .

[105]  Mark Bathe,et al.  A primer to scaffolded DNA origami , 2011, Nature Methods.

[106]  N. Seeman,et al.  A Proximity-Based Programmable DNA Nanoscale Assembly Line , 2010, Nature.

[107]  Petra Krystek,et al.  Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. , 2008, Biomaterials.

[108]  Hari K. K. Subramanian,et al.  The label-free unambiguous detection and symbolic display of single nucleotide polymorphisms on DNA origami. , 2011, Nano letters.

[109]  Friedrich C. Simmel,et al.  Membrane-Assisted Growth of DNA Origami Nanostructure Arrays , 2015, ACS nano.

[110]  Chad A Mirkin,et al.  Spherical nucleic acids. , 2012, Journal of the American Chemical Society.

[111]  Jie Chao,et al.  DNA origami-based shape IDs for single-molecule nanomechanical genotyping , 2017, Nature Communications.

[112]  Hao Yan,et al.  DNA origami as a carrier for circumvention of drug resistance. , 2012, Journal of the American Chemical Society.

[113]  Hendrik Dietz,et al.  Specific growth rate and multiplicity of infection affect high‐cell‐density fermentation with bacteriophage M13 for ssDNA production , 2017, Biotechnology and bioengineering.

[114]  H. Day,et al.  i-Motif DNA: structure, stability and targeting with ligands. , 2014, Bioorganic & medicinal chemistry.

[115]  F. Simmel,et al.  DNA-based self-assembly of chiral plasmonic nanostructures with tailored optical response , 2011, Nature.

[116]  William M. Shih,et al.  Virus-Inspired Membrane Encapsulation of DNA Nanostructures To Achieve In Vivo Stability , 2014, ACS nano.

[117]  N. Seeman De novo design of sequences for nucleic acid structural engineering. , 1990, Journal of biomolecular structure & dynamics.

[118]  S. Shinkai,et al.  Sol-gel reaction using DNA as a template: an attempt toward transcription of DNA into inorganic materials. , 2004, Angewandte Chemie.

[119]  H. Ju,et al.  Collapse of DNA Tetrahedron Nanostructure for "Off-On" Fluorescence Detection of DNA Methyltransferase Activity. , 2017, ACS applied materials & interfaces.

[120]  P. Rothemund Folding DNA to create nanoscale shapes and patterns , 2006, Nature.

[121]  Chunhai Fan,et al.  Functional DNA nanostructures for theranostic applications. , 2014, Accounts of chemical research.

[122]  C. Fan,et al.  DNA nanostructure-based universal microarray platform for high-efficiency multiplex bioanalysis in biofluids. , 2014, ACS applied materials & interfaces.

[123]  S. Howorka,et al.  A biomimetic DNA-based channel for the ligand-controlled transport of charged molecular cargo across a biological membrane. , 2016, Nature nanotechnology.

[124]  Almogit Abu-Horowitz,et al.  Universal computing by DNA origami robots in a living animal , 2014, Nature nanotechnology.

[125]  Jiye Shi,et al.  DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury , 2018, Nature Biomedical Engineering.

[126]  S. Howorka,et al.  Self-assembled DNA nanopores that span lipid bilayers. , 2013, Nano letters.

[127]  H. Pei,et al.  Self-assembled multivalent DNA nanostructures for noninvasive intracellular delivery of immunostimulatory CpG oligonucleotides. , 2011, ACS nano.

[128]  L. Manna,et al.  Metal-enhanced fluorescence of colloidal nanocrystals with nanoscale control , 2006, Nature nanotechnology.

[129]  Wen Jiang,et al.  In vivo production of RNA nanostructures via programmed folding of single-stranded RNAs , 2018, Nature Communications.

[130]  D. Leong,et al.  Clinically Relevant Detection of Streptococcus pneumoniae with DNA-Antibody Nanostructures. , 2017, Analytical chemistry.

[131]  Zhao Zhang,et al.  Vesicle Tubulation with Self-Assembling DNA Nanosprings. , 2018, Angewandte Chemie.

[132]  Jiye Shi,et al.  Hybridization chain reaction amplification of microRNA detection with a tetrahedral DNA nanostructure-based electrochemical biosensor. , 2014, Analytical chemistry.

[133]  Hao Yan,et al.  Dna Origami: a History and Current Perspective This Review Comes from a Themed Issue on Nanotechnology and Miniaturization Edited Structural Development Assembly Approaches Single-molecule Detection Material Organization , 2022 .

[134]  Lulu Qian,et al.  Asymmetric DNA Origami for Spatially Addressable and Index‐Free Solution‐Phase DNA Chips , 2010, Advanced materials.

[135]  N. Seeman,et al.  Programmable materials and the nature of the DNA bond , 2015, Science.

[136]  Luvena L. Ong,et al.  Three-Dimensional Structures Self-Assembled from DNA Bricks , 2012, Science.

[137]  P. Schwille,et al.  Membrane sculpting by curved DNA origami scaffolds , 2018, Nature Communications.

[138]  Erik Winfree,et al.  Molecular robots guided by prescriptive landscapes , 2010, Nature.

[139]  M. Bathe,et al.  Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures , 2011, Nucleic acids research.

[140]  Hao Yan,et al.  Tiamat: A Three-Dimensional Editing Tool for Complex DNA Structures , 2009, DNA.

[141]  Adam H. Marblestone,et al.  Rapid prototyping of 3D DNA-origami shapes with caDNAno , 2009, Nucleic acids research.

[142]  N. Seeman Nucleic acid junctions and lattices. , 1982, Journal of theoretical biology.

[143]  Hubing Shi,et al.  The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin. , 2006, Blood.

[144]  Pekka Orponen,et al.  DNA rendering of polyhedral meshes at the nanoscale , 2015, Nature.

[145]  Luc Jaeger,et al.  RNA self-assembly and RNA nanotechnology. , 2014, Accounts of chemical research.