This book reviews the structure-function relationship of nucleic acids, their role in the pathophysiology of the diseases, and as therapeutic targets for human diseases. The chapters discuss the role of nucleic acids in inflammatory diseases, neurodegenerative diseases, and cancer. The book also describes recent advancements in nucleic acid-based therapy, the application of nucleic acids in diagnostics, in the development of nano-carriers, logic gates, and sensors. It explores the use of nucleic acids (RNA and DNA) as a unique and multifunctional platform for numerous applications, including therapeutics, diagnostics, nanodevices, and materials. It further examines the role of DNA methylation, histone modifiers and readers, chromatin remodelers, microRNAs, and other components of chromatin in the progression of cancer. The book also discusses the applications of nucleic acid as a vaccine and as a gene-editing tool. It also provides an overview of the clinical trials using genome editing platforms for disease treatment and the challenges in implementing the editing technology. Finally, the book elucidates a representative description of challenges associated with nucleic acid-mediated therapy.
Author(s): Subhrangsu Chatterjee, Samit Chattopadhyay
Publisher: Springer
Year: 2023
Language: English
Pages: 422
City: Singapore
Preface
Contents
Editors and Contributors
1: Nucleic Acid Structure and Biology
1.1 Introduction
1.2 Nucleoside Conformation and Hydrogen Bonding
1.2.1 Sugar Conformation
1.2.2 Syn/Anti Conformation
1.2.3 Base Pair Arrangements
1.3 Double-Helical Nucleic Acids
1.3.1 A-, B-, and Z-Type Helices
1.3.2 Superhelicity and Superhelical Stress
1.4 Double-Helical Junctions in Nucleic Acids
1.4.1 Three-Way Junctions
1.4.1.1 Three-Way Junctions in Biology and Technology
1.4.2 Four-Way Junctions
1.4.2.1 Holliday Junctions
1.4.2.2 Cruciform Structures
1.4.2.3 Four-Way Junctions in Biology and Technology
1.5 Pseudoknots
1.5.1 Pseudoknots in Biology
1.6 Triple-Helical Structures
1.6.1 Intermolecular Triple Helices
1.6.2 H-DNA
1.6.3 Triplexes in Biology and Technology
1.7 The G-Quadruplex
1.7.1 Architecture of the G-Quadruplex Core
1.7.2 G-Quadruplex Topologies
1.7.3 G-Quadruplexes in Biology and Technology
1.8 The i-Motif
1.8.1 i-Motif Structures in Biology and Technology
1.9 Impact of Base Modifications on DNA Structure
1.10 Summary
References
2: Nucleic Acid-Mediated Inflammatory Diseases
2.1 Introduction
2.2 PRR Receptors
2.2.1 TLRs
2.2.1.1 TLR3
2.2.1.2 TLR9
2.2.1.3 TLR7
2.2.1.4 TLR8
2.2.1.5 TLR10 (in Humans)
2.2.1.6 TLR 13 (in Mouse)
2.2.2 NLRs
2.2.3 RLRs
2.2.4 ALRs
2.2.5 cGAS
2.2.6 Other Receptors
2.3 PRRs and Cell Death
2.3.1 Toll-like Receptors (TLR)
2.3.1.1 TLR9
2.3.1.2 TLR3
RIG-1-like Receptors (RLR)
Absent in Melanoma-2-like Receptors (ALRs)
IFI16
Intracellular DNA Sensors Such as cGAS
ZBP1
2.4 Nucleic Acid Sensors and Inflammatory Diseases
2.5 Autoimmune Disorders
2.5.1 Systemic Lupus Erythematosus (SLE)
2.5.2 Aicardi-Goutieres Syndrome (AGS)
2.5.3 Singleton-Merten Syndrome (SMS)
2.5.4 Rheumatoid Arthritis (RA)
2.5.5 Other Inflammatory Conditions
2.5.6 Nucleic Acid Sensors as Therapeutic Targets
2.5.7 Autoimmune Disorders
2.5.8 Infectious Disease
2.5.9 Cancer
2.6 Discussion
References
3: Alternative Splicing and Cancer
3.1 Introduction
3.2 Mechanisms of Alternative Splicing Regulation
3.3 Alternative Splicing of Non-coding RNAs
3.4 Relation Between Alternative Splicing and lncRNA
3.5 Relation Between Alternative Splicing and miRNA
3.6 Relation Between Alternative Splicing and siRNA
3.7 Relation Between Alternative Splicing and snoRNA
3.8 Dysregulation of Alternative Splicing in Cancer
3.8.1 Mutations in Cis-Regulatory Splice Sites
3.8.2 Mutations in Spliceosomal and Trans-Regulatory Splicing Factors
3.8.3 Alteration in Expression of Trans-Regulatory Splicing Factors
3.8.4 Alteration in Pathways Regulating Splicing Factors
3.9 Role of G-Quadruplex Motif at Splice Sites in the Regulation of Alternative Splicing
3.9.1 Alteration in Post-translational Modifications, Epigenetic Regulation, and Other Regulatory Mechanisms
3.10 Dysregulated Alternative Splicing and Hallmarks of Cancer
3.11 Modulation in Alternative Splicing as a Target for Cancer Detection and Therapeutics
3.11.1 Use of Antisense Oligos (ASOs) or Splicing-Switching Oligos (SSOs)
3.11.2 Use of Small Molecules
3.11.3 Use of Monoclonal Antibodies (mAbs) Targeting Deregulated Proteins
3.11.4 Use of Chemotherapeutic Drugs to Modify Splicing
3.11.5 Use of Spliceosome-Mediated RNA Trans-Splicing (SMaRT) Technique
References
4: Nucleic Acid-Based Strategies to Treat Neurodegenerative Diseases
4.1 Introduction
4.2 Technologies Under Nucleic Acid Therapeutics
4.2.1 Antisense Oligonucleotides (ASO)
4.2.1.1 Ligand-Modified Small Interfering RNA Conjugates
4.2.1.2 Anti-miRNA Oligonucleotides (antagoMIR)
4.2.1.3 Lipid Nanoparticles
4.2.1.4 Adeno-associated Virus Vectors
4.3 Strategies Involved in the Treatment of Neurodegenerative Disorders
4.3.1 Alzheimer´s Disease
4.3.2 Parkinson´s Disease
4.3.3 Huntington´s Disease
4.3.4 Spinal Muscular Atrophy
4.3.5 Frontotemporal Dementia (FTD)
4.3.6 Amyotrophic Lateral Sclerosis
4.4 Conclusion
References
5: Human Diseases Induced by Oxidative Damage in DNA
5.1 Introduction
5.2 Types of Oxidative Damage
5.2.1 Formation of 8-Oxo-G
5.2.2 Formation of 8-Nitro-G
5.3 Oxidative DNA Damage Repair Systems
5.3.1 Base Excision Repair (BER) Pathway
5.3.2 Nucleotide Excision Repair (NER) Pathway
5.4 Oxidative DNA Damage Can Disrupt Cellular Function
5.5 Human Diseases Induced by Oxidative DNA Damage
5.5.1 Oxidative Stress in Cancer Prognosis
5.5.2 In Neurodegenerative Diseases
5.5.3 In Inflammation/Infection
5.5.4 In Cardiovascular Diseases
5.5.5 Aging/Infertility and Metabolic Syndromes
5.5.6 Genetic Diseases Due to DDR Damage
5.6 Treatment of Diseases by Targeting DNA Damage and DDR Pathways
5.7 Conclusion
References
6: Nucleic Acid in Nanotechnology
6.1 Introduction
6.2 Structural DNA-Based Nanotechnologies
6.2.1 DNA Tiles
6.2.2 DNA Bricks
6.2.3 DNA Origami
6.2.4 DNA Crystals
6.2.5 DNA Nanotubes
6.2.6 DNA Hydrogel
6.3 Dynamic Self-Assembly Systems
6.3.1 Passive Assembly-Disassembly System
6.3.2 Trigger-Induced Autonomous Assembly Systems
6.3.3 Active Assembly Systems
6.3.4 Examples of Dynamic DNA Nanorobots
6.4 Modifications of DNA in Nanostructures
6.5 Nucleic Acid Analogues
6.6 Applications of DNA Nanotechnology
6.7 Summary
References
7: Nucleic Acid in Diagnostics
7.1 Introduction
7.2 Nucleic Acid Techniques in Molecular Diagnostics
7.2.1 Extraction of Nucleic Acids
7.2.1.1 Caesium Chloride/Ethidium Bromide Density Gradient Centrifugation
7.2.1.2 Phenol-Chloroform Extraction
7.2.1.3 Solid-Phase Extraction
7.2.1.4 Applications to Clinical Specimens
7.2.2 Nucleic Acid Amplification Techniques
7.2.2.1 Polymerase Chain Reaction
7.2.2.2 Transcription-Based Amplification Methods
7.2.2.3 Loop-Mediated Amplification Methods
7.2.2.4 Helicase-Dependent Amplification (HDA)
7.2.2.5 Signal-Mediated Amplification of RNA Technology (SMART)
7.2.2.6 Nucleic Acid Signal-Based Amplification (NASBA)
7.2.2.7 Recombinase Polymerase Amplification (RPA)
7.2.2.8 Rolling Circle Amplification (RCA)
7.2.2.9 Strand Displacement Amplification (SDA)
7.3 Nucleic Acid Testing for the Detection of Diseases
7.3.1 HIV-I
7.3.2 Cancer
7.3.3 Prenatal Testing
7.3.4 COVID-19
7.3.5 Infectious Diseases
7.4 Nucleic Acid in Personalized and Precision Medicine
7.5 Conclusion and Future Perspectives
References
8: Nucleic Acid Sensors and Logic Gates
8.1 Brief Overview to Biosensors
8.2 Fundamentals of Nucleic Acid Biosensor
8.2.1 Nucleic Acid Hybridization
8.2.2 Biosensors Based on Nucleic Acid Hybridization
8.3 Basic Design of Nucleic Acid Biosensors
8.3.1 Components of Nucleic Acid Biosensor
8.4 Recognition Elements of Nucleic Acid Biosensor
8.4.1 Aptamers
8.4.2 Riboswitches
8.4.3 DNAzymes
8.5 Types of Readouts in NA Biosensors
8.5.1 Optical Transducers
8.5.1.1 Fluorescent-Based Readout Biosensors
8.5.1.2 SPR Biosensor
8.5.1.3 Nano DLS Biosensor
8.5.2 Electrochemical Nucleic Acid Biosensors
8.5.3 Colorimetric Nucleic Acid Biosensor
8.5.4 Mass-Based Transducers
8.5.5 Piezoelectric Biosensor
8.6 Recent Development of Nucleic Acid Biosensors
8.7 Logic Gates: A Brief Introduction
8.8 Design of Logic Devices
8.8.1 Biomolecular Logic Devices
8.8.2 Nucleic Acid-Based Logic Devices
8.8.3 DNA Tetraplex-Based Logic Devices
8.8.4 Modes of Reuse of DNA Logic Devices for Continuous Operation
8.9 Association of DNA with Other Materials
8.10 Summary
References
9: Nucleic Acid Therapeutics in Cancer Biology
9.1 Introduction
9.2 RNAi Therapeutics
9.2.1 MicroRNA and siRNA
9.2.1.1 miRNA Mimics and antimiRs
9.2.1.2 ASOs
9.2.1.3 AntimiRs
9.2.1.4 Others
9.2.1.5 Delivery System of RNAi Therapeutics
9.2.1.6 Viral Vectors
9.2.1.7 Poly(Lactide-co-glycolide) Particles
Neutral Lipid Emulsions
Neutral Liposome 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine
EnGeneIC Delivery Vehicle Nanocells
Synthetic Polyethylenimine
Dendrimers
Cyclodextrin
Poly(Ethylene Glycol)
Chitosan
N-Acetyl-D-Galactosamine
9.3 Decoy Oligonucleotides
9.4 DNAzyme and RNAzymes
9.5 Conclusion and Future Perspectives
References
10: RNA Vaccines: The Evolution, Applications, and the Challenges Ahead
10.1 History of Vaccine
10.2 Introduction About Vaccination
10.3 Vaccines and Immunization
10.4 Types of Vaccines
10.5 Nucleic Acid (DNA) Vaccines at a Glance
10.6 Nucleic Acid Vaccines
10.7 RNA-Based Vaccines
10.8 Modifications of RNA Vaccines over Time
10.9 RNA Vaccines Against Viruses
10.10 RNA Vaccine and COVID-19
10.11 RNA Vaccine and Cancer
10.12 Limitations and Strategies to Tackle It
10.13 Conclusion
References
11: Nucleic Acid Editing
11.1 Contextual Background: Gene Editing
11.2 Methods in Nucleic Acid Editing: Meganuclease, ZFNs, and TALENs
11.3 CRISPR: From Adaptive Immunity to Genome Editing
11.4 Classification of the CRISPR-Cas Systems
11.5 Structural and Functional Insights of SpCas9
11.6 DNA Base Editing
11.7 RNA Targeting and Single-Base RNA Editing
11.8 Modular CRISPR System
11.8.1 Regulation of Cas9 Protein
11.8.1.1 Evolved or Engineered Cas9 Proteins
11.8.1.2 Transcriptionally Controlled Cas9
Tet System
Cre Dependent System
11.8.1.3 Small Molecule-Controlled CRISPR System
CIP Systems
Intein Splicing System
Systems Based on 4-OHT-ER Mediated Nuclear Translocation
Genetic Code Expansion
11.8.1.4 Light-Controlled Cas9 System
Light-Coupled Split Cas9
11.8.2 Regulation of gRNA
11.8.2.1 Engineering of gRNA
Spacer Length Optimization
Modified RNA
Toehold Switches
11.8.2.2 Small Molecule-Controlled gRNA
11.8.2.3 Light-Controlled gRNA
11.9 Gene Therapy Applications: Somatic Cells
11.10 Germline Editing and Active Genetics
References
