Genome Editing in Drug Discovery (eBook)

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.

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
Sasa Svikovic

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