The Aptamer Handbook

The Aptamer Handbook : Functional Oligonucleotides and Their Applications

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Description

In "The Aptamer Handbook", leading scientists from academia as well as biotech and pharma companies introduce the revolutionary concept of designing RNA and DNA oligonucleotides with novel functions by in vitro selection. These functions comprise high affinity binding (aptamers), catalytic activity (ribozymes and deoxyribozymes) or combinations of binding and catalytic properties (aptazymes). Basic concepts and technologies describing in detail how these functional oligonucleotides can be identified are presented. Numerous examples demonstrate the versatility of in vitro selected oligonucleotides. Special emphasis has been put on a section that shows the broad applicability of aptamers, e.g. in target validation, for analytics, or as new therapeutics. This first overview in the field is of prime interest for a broad audience of scientists both in academia and in industry who wish to expand their knowledge on the potential of new oligonucleotide functions and their applications.show more

Product details

  • Digital | 521 pages
  • Wiley-VCH Verlag GmbH
  • Weinheim, Germany
  • 3527608192
  • 9783527608195

Author information

Sven Klussmann is co-founder and Chief Scientific Officer of NOXXON Pharma AG, Berlin. He is a Biochemist by training and his initial studies were carried out at the Freie Universitat Berlin, where he obtained his academic degrees. Dr. Klussmann received the Carl Ramsauer Award for his dissertation in which he demonstrated the principles of the Spiegelmer Technology, a new approach to identify biostable mirror-image oligonucleotides (so-called Spiegelmers) that can bind with high affinity to target molecules. He has authored more than 30 articles and 40 patents on oligonucleotides and their applications.show more

Table of contents

Part 1: History and Theoretical Background.1 In Vitro Selection of Functional Oligonucleotides and the Origins of Biochemical Activity (James M. Carothers and Jack W. Szostak).1.1 Introduction.1.2 A Brief History of In Vitro Selection.1.3 Lessons from the Aptamers, Ribozymes, Deoxyribozymes Generated by In Vitro Selection.1.4 Synthetic Approaches to Understanding the Natural Origins of Function.1.5 Recent Technological Developments and Future Directions.1.6 Conclusion.2 Mathematical Models on RNA Evolution, Simulations In Silico, and Concepts for In Vitro Selection (Peter Schuster).2.1 From Early Experiments and Theories to the Concept of Neutral Networks.2.2 RNA Structures, Thermodynamics and Kinetic Folding.2.3 Neutral Networks and In Silico Evolution of Molecules.2.4 Designed and Natural RNA Switches.2.5 Outlook on Future Problems in RNA Design.3 Fitness Landscapes, Error Thresholds, and Cofactors in Aptamer Evolution (Adam Kun, Marie-Christine Maurel, Mauro Santos, and Eors Szathmary).3.1 Introduction.3.2 Functionality Landscapes Inferred from Examples.3.3 Error Thresholds Inferred from Functional Landscapes: The "Realistic" Error Threshold of the Neurospora VS Ribozyme.3.4 Looking for Catalytic Partners: Cofactors and Aptamers.3.5 The Use of Coenzymes: From the RNA World to the Protein World via Translation and the Genetic Code.3.6 Outlook.Part 2: In Vitro Selection of Target-binding Oligonucleotides.4 Aptamers to Small Molecules (Heiko Fickert, Iris G. Fransson, and Ulrich Hahn).4.1 Introduction.4.2 Aptamers to Nucleotides/Nucleosides/Nucleobases.4.3 Aptamers to Cofactors.4.4 Aptamers to Amino Acids.4.5 Aptamers to Carbohydrates.4.6 Aptamers to Natural Products.4.7 Aptamers to Organic or Fluorescent Dyes.4.8 The Chimeric Approach for Aptamer Selection.4.9 Conclusion.5 Aptamers to Antibiotics (Christina Lorenz and Renee Schroeder).5.1 Introduction.5.2 RNA-binding Antibiotics.5.3 Aptamers to Tetracyclines.5.4 Aptamers to Streptomycin.5.5 Aptamers to Aminoglycosides.5.6 Aptamers to Chloramphenicol.5.7 Aptamers to the Peptide Antibiotic Viomycin.5.7.1 The Peptide Antibiotic Viomycin as a Primordial Lead Molecule.5.8 What Have We Learned From the Antibiotic-binding Aptamers?6 Aptamers to Proteins (Shahid M. Nimjee, Christopher P. Rusconi, and Bruce A. Sullenger).6.1 Introduction.6.2 Properties of Aptamers as Protein Inhibitors.6.3 Cytokines/Growth Factors.6.4 Nucleic Acid Binding Proteins.6.5 Serine Proteases.6.6 Antibodies/Immunoglobulins.6.7 Cell Surface Receptor/Cell Adhesion Molecules.6.8 Complement Proteins - Human Complement C5.6.9 Extracellular Membrane Protein - Tenascin-C.6.10 Lipoproteins - Human Non-pancreatic Secretory Phospholipase A2.6.11 Prion Proteins - Prion Protein PrPSc.6.12 Peptides.6.13 Conclusion.7 Aptamers to Nucleic Acid Structures (Jean-Jacques Toulme, Fabien Darfeuille, Carmelo Di Primo, and Eric Dausse).7.1 Introduction.7.2 Targeting Double-stranded Nucleic Acids.7.3 Loop-Loop Interactions.7.4 Chemically Modified Aptamers Recognizing RNA Targets.7.5 Biological Properties of Aptamers Targeted to Nucleic Acids.7.6 Conclusion.8 Riboswitches: Natural Metabolite-binding RNAs Controlling Gene Expression (Adam Roth, Rdiger Welz, and Ronald R. Breaker).8.1 Introduction.8.2 Genetic Control by Riboswitches.8.3 Aptamer Domains of Riboswitches.8.4 Natural Aptamers Specific for Guanine and Adenine.8.5 High-resolution Aptamer Structures.8.6 The Glycine Riboswitch.Part 3: In Vitro Selection of Short, Catalytically Active Oligonucleotides.9 Catalytically Active RNA Molecules: Tools in Organic Chemistry (Barbara-Sylvia Weigand, Andreas Zerressen, Jrg C. Schlatterer, Mark Helm, and Andres Jaschke).9.1 Introduction.9.2 Catalytic Biopolymers.9.3 De Novo Creation of Ribozymes.9.4 The Catalytic Spectrum of Ribozymes.9.5 Summary and Outlook.10 Deoxyribozymes: Catalytically Active DNA Molecules (Kenny Schlosser, Simon A. McManus, and Yingfu Li).10.1 Initial Demonstration of DNA's Catalytic Ability.10.2 A Tale of Two Deoxyribozymes that Cleave RNA.10.3 Other Deoxyribozymes.10.4 Outlook.References.11 In Vivo and In Vitro Target Validation with Nucleic Acid Aptamers as Pharmacological Probes (P. Shannon Pendergrast and David M. Epstein).11.1 Introduction.11.2 Target Validation with Aptamers as Pharmacological Probes.11.3 Limitations of Target Validation by Gene or mRNA Knockout.11.4 Target Validation Using Nucleic Acid Aptamers.11.5 Summary.12 Intramers for Protein Function Analysis and Drug Discovery (Michael Famulok and Gnter Mayer).12.1 Introduction.12.2 Intramers: Intracellular Aptamers.12.3 Aptamers as Probes for Inhibitor Screening.12.4 Summary.13 Aptazymes: Allosteric Ribozymes and Deoxyribozymes as Biosensors (Scott M. Knudsen and Andrew D. Ellington).13.1 Introduction.13.2 Creating Aptazymes via Rational Design and In Vitro Selection Methodologies.13.3 Effector Activation.13.4 Aptazyme Structural and Functional Diversity.13.5 Uses of Aptazymes in Biology and Biotechnology.14 Conversion of Aptamers into Small-Molecule Lead Compounds (Andreas Jenne).14.1 Introduction.14.2 Rational Drug Design.14.3 Biochemical Screening.14.4 Summary and Outlook.15 Aptamers as Ligands for Affinity Chromatography and Capillary Electrophoresis Applications (Eric Peyrin).15.1 Introduction.15.2 Aptamers as Ligands in Affinity Liquid Chromatography (and Electrochromatography).15.3 Aptamers as Ligands in Affinity Capillary Electrophoresis.15.4 Concluding Remarks.16 Aptamers for In Vivo Imaging (Sandra Borkowski and Ludger M. Dinkelborg).16.1 In Vivo Imaging: Modalities and Requirements.16.2 Aptamers for In Vivo Imaging.16.3 Labeling of Aptamers.16.4 Oligonucleotides in SPECT and PET Imaging.16.5 Outlook.17 Properties of Therapeutic Aptamers (Sharon T. Cload, Thomas G. McCauley, Anthony D. Keefe, Judith M. Healy, and Charles Wilson).17.1 Introduction.17.2 Aptamer Targets.17.3 Aptamer Binding Characteristics.17.4 Chemical Modification of Aptamers.17.5 Routes of Administration of Aptamers.17.6 Opportunities for Alternative Aptamer Formulations.17.7 Aptamer Pharmacokinetics and Biodistribution.17.8 Toxicity Profile of Aptamers.17.9 Immunogenicity of Aptamers.17.10 Aptamer Manufacture.17.11 Examples of Therapeutic Aptamers in Development.17.12 Future Prospects for Aptamer Therapeutics.18 Spiegelmers for Therapeutic Applications - Use of Chiral Principles in Evolutionary Selection Techniques (Dirk Eulberg, Florian Jarosch, Stefan Vonhoff, and Sven Klussmann).18.1 Evolutionary Selection Techniques.18.2 Chirality.18.3 Mirror-Image Evolutionary Techniques: Selection-Reflection.18.4 Summary.19 Applications in the Clinic: The Anti-VEGF Aptamer (Tony Realini, Eugene W.M. Ng, and Anthony P. Adamis).19.1 Introduction.19.2 Rationale for Targeting VEGF.19.3 VEGF and Human Disease.19.4 The VEGF Therapeutic Dilemma.19.5 VEGF Inhibition.19.6 Enter Macugen.19.7 The Future.Epilogue A Personal Perspecitve: Aptamers after 15 Years (Larry Gold).The Beginning.The First Patent.Creation of NeXagen and NeXstar.Diagnostic Imaging.Aptamer Therapeutics.Aptamer-based Diagnostics at SomaLogic.Do Natural Aptamers Exist?Conclusions - SELEX Lessons for Drug Discovery.Index.show more

Review quote

"Insgesamt gesehen ist das Buch...hervorragend. Fur Forscher auf dem Gebiet der Aptamere wird es mit Recht zu dem Nachschlagewerk avancieren. Klare Abbildungen, eine ausfuhrliche Liste mit Literaturhinweisen in jedem Kapitel und ein detailliertes Sachwortverzeichnis erganzen die ausgezeichnete Darstellung der Themen. Studierende wie auch fortgeschrittene Wissenschaftler werden von der Lekture profitieren." Angewandte Chemieshow more