Aptamer Handbook introduces the revolutionary concept of designing RNA and DNA oligonucleotides with novel functions by in vitro selection.

Features:

• Compromises high affinity binding (aptamers), catalytic activity (ribozymes and deoxyribozymes) or combinations of binding and catalytic properties (aptazymes).
• Includes basic concepts and technologies describing in detail how functional oligonucleotides can be identified
• Details numerous examples that demonstrate the versatility of in vitro selected oligonucleotides

Contents

In Vitro Selection of Functional Oligonucleotides and the Origins of Biochemical Activity

• A Brief History of In Vitro Selection
• Lessons from the Aptamers, Ribozymes, Deoxyribozymes Generated by In Vitro Selection
• Synthetic Approaches to Understanding the Natural Origins of Function
• Recent Technological Developments and Future Directions

Mathematical Models on RNA Evolution, Simulations In Silico, and Concepts for In Vitro Selection

• From Early Experiments and Theories to the Concept of Neutral Networks
• RNA Structures, Thermodynamics and Kinetic Folding
• Neutral Networks and In Silico Evolution of Molecules
• Designed and Natural RNA Switches
• Outlook on Future Problems in RNA Design

Fitness Landscapes, Error Thresholds, and Cofactors in Aptamer Evolution

• Functionality Landscapes Inferred from Examples
• Error Thresholds Inferred from Functional Landscapes: The “Realistic” Error Threshold of the Neurospora VS Ribozyme
• Looking for Catalytic Partners: Cofactors and Aptamers
• The Use of Coenzymes: From the RNA World to the Protein World via Translation and the Genetic Code
• In Vitro Selection of Target-binding Oligonucleotides

Aptamers to Small Molecules

• Aptamers to Nucleotides/Nucleosides/Nucleobases
• Aptamers to Cofactors
• Aptamers to Amino Acids
• Aptamers to Carbohydrates
• Aptamers to Natural Products
• Aptamers to Organic or Fluorescent Dyes
• The Chimeric Approach for Aptamer Selection

Aptamers to Antibiotics

• RNA-binding Antibiotics
• Aptamers to Tetracyclines
• Aptamers to Streptomycin
• Aptamers to Aminoglycosides
• Aptamers to Chloramphenicol
• Aptamers to the Peptide Antibiotic Viomycin
• The Peptide Antibiotic Viomycin as a Primordial Lead Molecule
• What Have We Learned From the Antibiotic-binding Aptamers

Aptamers to Proteins

• Properties of Aptamers as Protein Inhibitors
• Cytokines/Growth Factors
• Nucleic Acid Binding Proteins
• Serine Proteases
• Antibodies/Immunoglobulins
• Cell Surface Receptor/Cell Adhesion Molecules
• Complement Proteins – Human Complement C5
• Extracellular Membrane Protein – Tenascin-C
• Lipoproteins – Human Non-pancreatic Secretory Phospholipase A2
• Prion Proteins – Prion Protein PrP^Sc
• Peptides

Aptamers to Nucleic Acid Structures

• Targeting Double-stranded Nucleic Acids
• Loop–Loop Interactions
• Chemically Modified Aptamers Recognizing RNA Targets
• Biological Properties of Aptamers Targeted to Nucleic Acids

Riboswitches: Natural Metabolite-binding RNAs Controlling Gene Expression

• Genetic Control by Riboswitches
• Aptamer Domains of Riboswitches
• Natural Aptamers Specific for Guanine and Adenine
• High-resolution Aptamer Structures
• The Glycine Riboswitch

Catalytically Active RNA Molecules: Tools in Organic Chemistry

• Catalytic Biopolymers
• De Novo Creation of Ribozymes
• The Catalytic Spectrum of Ribozymes

Deoxyribozymes: Catalytically Active DNA Molecules

• Initial Demonstration of DNA’s Catalytic Ability
• A Tale of Two Deoxyribozymes that Cleave RNA
• Other Deoxyribozymes

In Vivo and In Vitro Target Validation with Nucleic Acid Aptamers as Pharmacological Probes

• Target Validation with Aptamers as Pharmacological Probes
• Limitations of Target Validation by Gene or mRNA Knockout
• Target Validation Using Nucleic Acid Aptamers

Intramers for Protein Function Analysis and Drug Discovery

• Intramers: Intracellular Aptamers
• Aptamers as Probes for Inhibitor Screening

Aptazymes: Allosteric Ribozymes and Deoxyribozymes as Biosensors

• Creating Aptazymes via Rational Design and In Vitro Selection Methodologies
• Effector Activation
• Aptazyme Structural and Functional Diversity
• Uses of Aptazymes in Biology and Biotechnology

Conversion of Aptamers into Small-Molecule Lead Compounds

• Rational Drug Design
• Biochemical Screening

Aptamers as Ligands for Affinity Chromatography and Capillary Electrophoresis Applications

• Aptamers as Ligands in Affinity Liquid Chromatography (and Electrochromatography)
• Aptamers as Ligands in Affinity Capillary Electrophoresis

Aptamers for In Vivo Imaging

• In Vivo Imaging: Modalities and Requirements
• Aptamers for In Vivo Imaging
• Labeling of Aptamers
• Oligonucleotides in SPECT and PET Imaging
• Outlook

Properties of Therapeutic Aptamers

• Aptamer Targets
• Aptamer Binding Characteristics
• Chemical Modification of Aptamers
• Routes of Administration of Aptamers
• Opportunities for Alternative Aptamer Formulations
• Aptamer Pharmacokinetics and Biodistribution
• Toxicity Profile of Aptamers
• Immunogenicity of Aptamers
• Aptamer Manufacture
• Examples of Therapeutic Aptamers in Development
• Future Prospects for Aptamer Therapeutics

Spiegelmers for Therapeutic Applications – Use of Chiral Principles in Evolutionary Selection Techniques

• Evolutionary Selection Techniques
• Chirality
• Mirror-Image Evolutionary Techniques: Selection–Reflection

Applications in the Clinic: The Anti-VEGF Aptamer

• Rationale for Targeting VEGF
• VEGF and Human Disease
• The VEGF Therapeutic Dilemma
• VEGF Inhibition
• Enter Macugen

Index

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