GENOME EDITING IN DRUG DISCOVERY
A practical guide for researchers and professionals applying genome editing techniques to drug discovery
In Genome Editing in Drug Discovery, a team of distinguished biologists delivers a comprehensive exploration of genome editing in the drug discovery process, with coverage of the technology’s history, current issues and techniques, and future perspectives and research directions. The book discusses techniques for disease modeling, target identification with CRISPR, safety studies, therapeutic editing, and intellectual property issues.
The safety and efficacy of drugs and new target discovery, as well as next-generation therapeutics are also presented.
Offering practical suggestions for practitioners and academicians involved in drug discovery, Genome Editing in Drug Discovery is a fulsome treatment of a technology that has become part of nearly every early step in the drug discovery pipeline. Selected contributions also include:
A thorough introduction to the applications of CRISPRi and CRISPRa in drug discovery Comprehensive explorations of genome-editing applications in stem cell engineering and regenerative medicine Practical discussions of the safety aspects of genome editing with respect to immunogenicity and the specificity of CRISPR-Cas9 gene editing In-depth examinations of critical socio-economic and bioethical challenges in the CRISPR-Cas9 patent landscape
Perfect for academic researchers and professionals in the biotech and pharmaceutical industries, Genome Editing in Drug Discovery will also earn a place in the libraries of medicinal chemists, biochemists, and molecular biologists.
Preface vii List of Abbreviations viii List of Contributors ix Part 1 Introduction to Drug Discovery and Genome Editing Methods 1 1 Genome Editing in Drug Discovery 3 Steve Rees 2 Historical Overview of Genome Editing from Bacteria to Higher Eukaryotes 9 Marcello Maresca 3 CRISPR Cas: From Bacterial Adaptive Immunity to the Swiss Army Knife of Drug Discovery 19 Saša Šviković 4 Commercially Available Reagents and Contract Research Services for CRISPR-Based Studies 47 Klio Maratou, Aaron T. Cheng, Fiona M. Behan, Ning Sun, and Quinn Lu 5 Computational Tools for Target Design and Analysis 61 Gue-Ho Hwang and Sangsu Bae Part 2 Genome Editing in Disease Modeling 73 6 Genome Editing in Cellular Disease Models 75 Pierre Theurey, Kader Thiam, Yacine Chérifi, Alexandre Fraichard, and Amélie Rezza 7 Utilizing CRISPR/Cas9 Technologies for in vivo Disease Modeling and Therapy 93 Lukas Badertscher and Michelle J. Porritt Part 3 Genome Editing in Target Identification and Validation 111 8 Pooled CRISPR KO Screens for Target Identification 113 Antje Grotz and Sumit Deswal 9 Functional Genomics: Arrayed CRISPR KO Screens 127 Davide Gianni and Leire Escudero-Ibarz 10 Applications of CRISPRi and CRISPRa in Drug Discovery 139 Luke A. Gilbert 11 Sequence Diversification Screens with CRISPR-Cas9-Guided Base Editors 151 Jenna Persson and Bernhard Schmierer 12 Single-Cell Transcriptomics and Epigenomics for CRISPR-Mediated Perturbation Studies 165 Saumyaa Saumyaa, Ramy Elgendy, and Alessandro Bonetti Part 4 Therapeutic Genome Editing 175 13 DNA Repair Pathways in the Context of Therapeutic Genome Editing 177 Sandra Wimberger, Nina Akrap, and Amir Taheri-Ghahfarokhi 14 DNA Base Editing Strategies for Genome Editing 193 Matthew Coelho, Songyuan Li, and Benjamin JM Taylor 15 RNA Base Editing Technologies for Gene Therapy 203 Sumit Deswal 16 Genome Editing Applications in Cancer T Cell Therapy 213 William A. Nyberg and Justin Eyquem 17 Genome-Editing Applications in Stem Cell Engineering and Regenerative Medicine 231 Pragya Gupta, Shashank Jaitly, Priya Thakur, Sangam Giri Goswami, Nupur Bhargava, and Sivaprakash Ramalingam 18 Delivery and Formulation Methods for Therapeutic Genome Editing 261 Erik Oude Blenke and Venkata R. Krishnamurthy 19 Safety Aspects of Genome Editing: Immunogenicity 281 Rakesh Kantilal Chandode and Roberto Nitsch 20 Specificity of CRISPR-Cas9 Gene Editing 289 Niklas Selfjord, Alexandra Madsen, and Pinar Akcakaya Part 5 Intellectual Property Aspects and Future Prospects 313 21 Key Socio-Economic and (Bio)Ethical Challenges in the CRISPR-Cas9 Patent Landscape 315 Franc Mali 22 Emerging Technologies for Genome Editing 329 Martin Peterka Index 337
Marcello Maresca, PhD, is a Senior Director in the Discovery Sciences Department at AstraZeneca. He obtained his doctorate in Molecular Biology from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany. Sumit Deswal, PhD, is an Associate Principal Scientist with the Genome Engineering Team at AstraZeneca R&D in Sweden. He obtained his doctorate in Immunology from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany.
