DNA Nanotechnology for Cell Research

Preface xv Part I DNA Nanotechnology for Cellular Recognition (Cell SELEX, Cell Surface Engineering) 1 1 Developing DNA Aptamer Toolbox for Cell Research 3 Liang Yue, Shan Wang, and Weihong Tan 1.1 Cells and Their Complexity 3 1.2 Features and Advantages of DNA Aptamers 4 1.3 On-demand Synthesis and Screening of DNA Aptamers 5 1.4 Toward a Toolbox of DNA Aptamers for Cellular Applications 9 1.4.1 Chemical Modifications via Solid-Supported Synthesis Strategy 10 1.4.2 Chemical Modifications Through Covalent Conjugation 13 1.4.3 Self-assembly Systems Based on Chemically Modified DNA Aptamers 15 1.4.4 DNA Aptamers Engineered with Nanotechnology 19 1.5 Summary and Outlook 21 Acknowledgments 22 References 22 2 Bacterial Detection with Functional Nucleic Acids: Escherichia coli as a Case Study 31 Yash Patel and Yingfu li 2.1 General Introduction to Bacteria 31 2.2 E. coli 32 2.3 Conventional Methods for General E. coli Detection 33 2.3.1 Sorbitol MacConkey Agar 34 2.3.2 Pcr 34 2.4 Biosensors for E. coli Detection 35 2.4.1 Protein Biosensors for E. coli Detection 35 2.4.2 Functional Nucleic Acid-Based Sensors for E. coli Detection 36 2.5 Conclusion 41 References 42 3 From Ligand-Binding Aptamers to Molecular Switches 47 Sanshu Li, Xiaojun Zhang, Tao Luo, Xuejiao Liu, Tingting Zhai, and Hongzhou Gu 3.1 Aptamers Can Be Generated by SELEX 47 3.2 Various Subtypes of SELEX Have Been Invented 48 3.3 Riboswitches Are Natural RNA Aptamers Carrying Expression Platforms 49 3.4 Riboswitches Use Various Mechanisms to Regulate Gene Expression 52 3.5 Riboswitches Are Potential Drug Targets 55 3.6 Fusing Aptamer with Expression Platform to Construct Artificial RNA Switches 55 3.7 Conclusions 57 Acknowledgments 57 References 57 4 DNA Nanotechnology-Based Microfluidics for Liquid Biopsy 63 Qi Niu, Shanqing Huang, Chaoyong Yang, and Lingling Wu 4.1 Introduction 63 4.2 DNA Nanotechnology-Based Microfluidics for Isolation of Circulating Targets 65 4.2.1 Aptamer-Modified Micro/Nano-Substrate Microfluidic Chip 65 4.2.2 DNA Framework-Supported Affinity Substrate Microfluidic Chip 73 4.3 DNA Nanotechnology-Based Microfluidics for Release and Detection of Circulating Targets 77 4.3.1 Efficient Release 77 4.3.2 Analysis and Destruction of CTCs 81 4.3.3 Sensitive Detection of EVs 85 4.4 DNA-Assisted Microfluidics for Single-Cell/Vesicle Analysis 88 4.4.1 Single-Cell Analysis by Sequencing 89 4.4.2 Single-Cell Analysis by Spectroscopy 93 4.4.3 Single-Vesicle Analysis 95 4.5 Summary and Outlook 97 References 98 5 Spatiotemporal-Controlled Cell Membrane Engineering Using DNA Nanotechnology 105 Wenxue Xie, Cong Ren, Minjie Lin, and Hang Xing 5.1 Background 105 5.2 DNA Modifications on the External Cell Membrane Surface 107 5.2.1 Strategies to Incorporate DNA onto External Cell Membrane Surface 107 5.2.2 Applications of External Membrane-modified DNA 114 5.3 DNA Modifications on the Internal Cell Membrane Surface 120 5.3.1 Transmembrane Modification of DNA 121 5.3.2 Inner Leaflet Modification Approaches 124 5.3.3 Liposome Fusion-Based Transport (LiFT) Approach 129 5.4 Perspectives 130 Acknowledgments 132 References 132 Part II Dna Nanotechnology for Cell Imaging and Intracellular Sensing 141 6 Metal-Dependent DNAzymes for Cell Surface Engineering and Intracellular Bioimaging 143 Ruo-Can Qian, Yuting Wu, Zhenglin Yang, Weijie Guo, Ze-Rui Zhou, andYiLu 6.1 Cellular Surface Engineering and Intracellular Bioimaging Show Great Potential in Biological and Medical Research 143 6.2 Metal-Specific DNAzymes: A Suitable Choice for Artificial Manipulation of Living Cells 144 6.3 Cell Surface Engineering by Programmable DNAzymes 145 6.3.1 Cell Surface Engineering Using DNAzyme-Based Control Switches 145 6.3.2 Dynamic Inter- and Intra-Cellular Regulation Using Engineered DNAzyme Molecular Machines 147 6.3.3 Cell Surface Imaging of Extracellular Signaling Molecule Using DNAzyme Sensors 149 6.4 Intracellular Imaging of Metal Ions with DNAzyme-Based Biosensors 150 6.4.1 DNAzyme-Based Catalytic Beacon for Intracellular Imaging 150 6.4.2 Caged DNAzymes for Temporally Controlled Imaging 154 6.4.3 DNAzyme-Based Sensing with Signal Amplification 159 6.4.4 Genetically Encoded Sensors for Metal Sensing in Living Cells 159 6.5 Conclusion 161 Acknowledgments 161 References 161 7 DNA Nanomotors for Bioimaging in Living Cells 169 Hanyong Peng, Aijiao Yuan, Hang Xiao, Zi Ye, Lejun Liao, Shulin Zhao, and X. Chris Le References 184 8 Illuminating RNA in Live Cells with Inorganic Nanoparticles-Based DNA Sensor Technology 189 Fangzhi Yu, Xiangfei li, Xiulin Yi, and Lele li 8.1 RNA Detection and Imaging 189 8.2 RNA Imaging Based on Direct Hybridization 190 8.3 RNA Imaging Based on Strand Displacement Reactions 192 8.4 Signal-amplified RNA Imaging 194 8.4.1 HCR-Based DNA Nanosensors for Amplified RNA Imaging 194 8.4.2 CHA-Based DNA Nanosensors for Amplified RNA Imaging 196 8.4.3 Amplified RNA Imaging Based on DNA Nanomachines 198 8.5 Spatiotemporally Controlled RNA Imaging in Live Cells 203 8.6 Conclusion 206 Acknowledgment 207 References 207 9 Building DNA Computing System for Smart Biosensing and Clinical Diagnosis 211 Jiao Yang and Da Han 9.1 DNA Computing 211 9.1.1 DNA Logic Gates Based on Functional DNA Motifs 212 9.1.2 DNA Logic Gates Based on DNA Cascading Reactions 215 9.2 DNA-Based Computing Devices for Biosensing 217 9.2.1 In Vitro Biosensing 217 9.2.2 Cellular Biosensing 220 9.3 DNA Computing for Clinical Diagnosis 223 9.4 Conclusion 226 References 226 10 Intelligent Sense-on-Demand DNA Circuits for Amplified Bioimaging in Living Cells 233 Yuqiu He, Zeyue Wang, Yuqian Jiang, and Fuan Wang 10.1 DNA Circuit: The Promising Technique for Bioimaging 233 10.2 Nonenzymatic DNA Circuits 234 10.2.1 Hybridization Chain Reaction (HCR) 234 10.2.2 Catalytic Hairpin Assembly (CHA) 235 10.2.3 Entropy-Driven DNA Catalytic Reaction (EDR) 236 10.2.4 DNAzyme-Powered Catalytic Reaction (DZR) 236 10.3 Intelligent Integrated DNA Circuits for Amplified Bioimaging 237 10.3.1 Hybridization-Dependent Cascade DNA Circuits 237 10.3.2 DNAzyme-Assisted Tandem DNA Circuits 239 10.3.3 Autocatalysis-Driven Feedback DNA Circuits 241 10.4 Stimuli-Responsive DNA Circuits for Reliable Bioimaging 243 10.4.1 Photo-Responsive DNA Circuits for Amplified Bioimaging 243 10.4.2 Enzyme-Activated DNA Circuits for Amplified Bioimaging 245 10.4.3 RNA-Stimulated DNA Circuits for Amplified Bioimaging 246 10.4.4 Other Strategies for Regulating DNA Circuits 249 10.5 Conclusion and Perspectives 251 Acknowledgments 252 References 252 11 DNA Nanoscaffolds for Biomacromolecules Organization and Bioimaging Applications 259 Yuanfang Chen, Jiayi Li, and Yuhe R. Yang 11.1 Introduction 259 11.2 Assembly of DNA-Scaffolded Biomacromolecules 259 11.3 Application of DNA Nanoscaffold for Regulation of Enzyme Cascade Reaction 261 11.3.1 Distance Control of Enzyme Cascade 261 11.3.2 Enzyme Compartmentalization 263 11.3.3 Directed Substrate Channeling with Swinging Arms 264 11.3.4 Scaffolded Enzyme Cascade in Living Cells 265 11.4 DNA Nanostructures Empowered Bioimaging Technologies 267 11.4.1 DNA Nanostructures Scaffolded Fluorophore Expansion 267 11.4.2 DNA-PAINT-Based Super-Resolution Fluorescence Imaging 269 11.4.3 DNA Nanostructures-Assisted Cryogenic Electron Microscopy Characterization 269 11.5 Summary and Outlook 270 References 271 Part III Dna Nanotechnology for Regulation of Cellular Functions 279 12 Adopting Nucleic Acid Nanotechnology for Genetic Regulation In Vivo 281 Friedrich C. Simmel 12.1 Introduction 281 12.2 Toehold-Mediated Strand Displacement: Switching Nucleic Acids with Nucleic Acids 282 12.3 Toehold Riboregulators and Related Systems 283 12.3.1 Riboswitches 283 12.3.2 Translational Switching with Toehold Switches 284 12.3.3 Toehold Switching in Eukaryotes 285 12.3.4 Transcriptional Switching 286 12.3.5 Applications as Sensors 286 12.3.6 Applications in Biocomputing 287 12.4 Applying Nucleic Acid Nanotechnology to CRISPR and RNA Interference 288 12.4.1 CRISPR Techniques 288 12.4.2 Switchable Guide RNAs 289 12.4.3 Implementing More Complex Programs in Mammalian Cells 291 12.4.4 Combining CRISPR with Origami 292 12.4.5 MicroRNAs and RNA Interference 292 12.5 Delivery of Nucleic Acid Devices, In Vivo Production, and Challenges for In Vivo Operation 293 12.5.1 Delivery 293 12.5.2 In Vivo Production 293 12.5.3 Challenges 294 12.6 Conclusion and Outlook 294 Acknowledgments 295 References 295 13 Cell Membrane Functionalization via Nucleic Acid Tools for Visualization and Regulation of Cellular Receptors 303 Shan Chen, Jingying Li, and Huanghao Yang 13.1 Nucleic Acid-Based Functionalization Strategies: From Receptor Information to DNA Probes 303 13.2 Uncovering Molecular Information of Cellular Receptors 307 13.3 Governing Cellular Receptors-Mediated Signal Transduction 313 13.4 Conclusion 318 Acknowledgments 318 References 318 14 Harnessing DNA Nanotechnology for Nongenetic Manipulation and Functionalization of Cell Surface Receptor 325 Hexin Nan, Hong-Hui Wang, and Zhou Nie 14.1 Introduction 325 14.2 Principle of DNA-enabled Molecular Engineering for Receptor Regulation 329 14.2.1 Recognition Module for Receptor Manipulation 330 14.2.2 Spatial Scaffold Module for Receptor Organization 330 14.2.3 Dynamic Assembly Module for Kinetic Control of Receptor 331 14.3 DNA Nanodevices for Programming Receptor Function 332 14.3.1 Bivalent Aptamer Mimicking Natural Ligand to Induce Receptor Dimerization 332 14.3.2 DNA Nanodevices to Customize Receptor Responsiveness 333 14.3.3 Light-Responsive DNA Nanodevices for Spatiotemporal Receptor Regulation 335 14.3.4 DNA Nanodevices for Visualization of Receptor Activation 337 14.4 Elaborate and Intelligent DNA Nanodevices Reprogramming Receptor Function 339 14.4.1 Mechanical Control Over Receptor-Mediated Cellular Behavior 339 14.4.2 Precise Cell Targeting for Selective Receptor Modulation 341 14.4.3 Spatial Organization of Nanoscale Receptor Distribution 344 14.5 Conclusions and Perspectives 347 Acknowledgments 348 References 348 15 DNA-Based Cell Surface Engineering for Programming Multiple Cell–Cell Interactions 355 Mingshu Xiao, Yueyang Sun, Li Li, and Hao Pei 15.1 DNA Nanotechnology: The Tool of Choice for Programming Cell–Cell Interactions 355 15.2 Modifying Cell Surface with DNA 356 15.3 Programming Cell–Cell Interactions by DNA Nanotechnology 359 15.3.1 Ligand–Receptor Binding-Based Cell–Cell Interactions 359 15.3.2 DNA Hybridization-Based Cell–Cell Interactions 362 15.3.3 DNA Circuit-Regulated Cell–Cell Interactions 364 15.4 Conclusion 366 Acknowledgments 367 References 367 16 Designer DNA Nanostructures and Their Cellular Uptake Behaviors 375 Jing Ye, Donglei Yang, Chenzhi Shi, Fei Zhou, and Pengfei Wang 16.1 Introduction 375 16.2 DNA Nanotechnology 376 16.2.1 The Beginning of DNA Nanotechnology 376 16.2.2 DNA Origami 377 16.2.3 Single-Stranded DNA Tiles 378 16.2.4 Dynamic DNA Structures 379 16.3 Pathways of Cell Endocytosis 381 16.3.1 Clathrin-Mediated Endocytosis 381 16.3.2 Clathrin-Independent Endocytosis 382 16.3.3 Phagocytosis 384 16.3.4 Macropinocytosis 384 16.3.5 Caveolin-Mediated Endocytosis 385 16.4 Analysis of DNA Nanostructures’ Cellular Uptake Behaviors 386 16.4.1 Effect of Size and Shape on Cellular Uptake 386 16.4.2 Effect of Surface Modifications on Cellular Uptake 389 16.4.3 Effect of Other Aspects on Cellular Uptake 392 References 395 Part IV Dna Nanotechnology for Cell-targeted Medical Applications 401 17 Toward Production of Nucleic Acid Nanostructures in Life Cells and Their Biomedical Applications 403 Mengxi Zheng, Victoria E. Paluzzi, Cuizheng Zhang, and Chengde Mao 17.1 DNA Nanostructures 403 17.1.1 Strategies of DNA Nanostructures Construction 403 17.1.2 Production of ssDNA Nanostructures in Living Cells 404 17.2 RNA Nanostructures 406 17.2.1 Strategies of RNA Nanostructures Construction 406 17.2.2 Production of ssRNA Nanostructures in Living Cells 407 17.3 Applications 409 17.4 Conclusion 412 References 412 18 Engineering Nucleic Acid Structures for Programmable Intracellular Biocomputation 415 Na Wu, Pengyan Hao, Chunhai Fan, and Yongxi Zhao References 432 19 DNA Supramolecular Hydrogels for Biomedical Applications 437 Ziwei Shi, Yuanchen Dong, and Dongsheng Liu 19.1 Introduction 437 19.2 Classification and Preparation of DNA Supramolecular Hydrogels 438 19.2.1 Pure DNA Supramolecular Hydrogels 438 19.2.2 Hybrid Supramolecular DNA Hydrogels 440 19.3 Biomedical Application of DNA Supramolecular Hydrogels 443 19.3.1 DNA Supramolecular Hydrogels for Bio-sensing 443 19.3.2 DNA Supramolecular Hydrogels for Drug Delivery 446 19.3.3 DNA Supramolecular Hydrogels for Immunotherapy 449 19.3.4 DNA Supramolecular Hydrogels for 3D Cell Culture 451 19.3.5 DNA Supramolecular Hydrogels for Tissue Engineering 454 19.4 Conclusions and Perspectives 458 References 459 20 Rolling Circle Amplification-Based DNA Nanotechnology for Cell Research 467 Nachuan Song, Yiwen Chu, Xun You, and Dayong Yang 20.1 Introduction 467 20.2 Principle and Synthetic Methods of RCA 468 20.2.1 Principle 468 20.2.2 DNA Hydrogel 469 20.2.3 DNA Nanoparticles 469 20.3 RCA-Based DNA Nanotechnology for Cell Separation 469 20.4 RCA-Based DNA Nanotechnology for Nucleic Acid Drug Delivery 475 20.5 Conclusion 484 Acknowledgment 485 References 485 21 Precise Integration of Therapeutics in DNA-Based Nanomaterials for Cancer Treatments 489 Yimeng Li, Lijuan Zhu, and Chuan Zhang 21.1 DNA-Based Nanomaterials in Biomedicine 490 21.1.1 Properties of DNA-Based Nanomaterials 491 21.1.2 Architectures of DNA-Based Nanomaterials 492 21.1.3 Interactions Between DNA-Based Drug Delivery Systems (DDSs) and Cells 495 21.2 Strategies on Constructing DNA-Based DDSs 498 21.2.1 DNA-Based DDSs Engineered Through Non-covalent Interactions 499 21.2.2 DNA-Based DDSs Engineered Through Covalent Interactions 502 21.3 Precise Integration of Therapeutics into DNA-Based DDSs to Achieve Synergistic Cancer Treatment 507 21.3.1 Chemogenes 507 21.3.2 Chemogene-Based DNA Nanomaterials 508 References 511 Index 515