PA, USA
Yacine Chérifi genOway, Lyon, France
Matthew Coelho Wellcome Sanger Institute, Cambridge, UK
Sumit Deswal Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Ramy Elgendy Translational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Molndal, Sweden
Leire Escudero‐Ibarz Discovery Biology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
Justin Eyquem Gladstone‐UCSF Institute of Genomic Immunology, San Francisco, CA, USADivision of Hemato‐Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USAandDepartment of Microbiology and Immunology & Parker Institute of Cancer Immunotherapy, University of California San Francisco, San Francisco, CA, USA
Alexandre Fraichard genOway, Lyon, France
Davide Gianni Discovery Biology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
Luke A. Gilbert Departments of Urology and Cellular & Molecular Pharmacology, and UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
Sangam Giri Goswami Genomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India
Antje Grotz Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Pragya Gupta Genomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India
Gue‐Ho Hwang Department of Chemistry and Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul, South Korea
Shashank Jaitly Genomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India
Venkata R. Krishnamurthy Advanced Drug Delivery, Pharmaceutical Sciences, AstraZeneca R&D, Boston, MA, USA
Songyuan Li Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Quinn Lu Novel Human Genetics Research Unit, R&D GlaxoSmithKline, Upper Providence, PA, USA
Alexandra Madsen Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Franc Mali Faculty of Social Sciences, University of Ljubljana, Ljubljana, Slovenia
Klio Maratou Functional Genomics, R&D GlaxoSmithKline, Stevenage, UK
Marcello Maresca Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Roberto Nitsch Gene Therapy, Functional and Mechanistic Safety, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
William A. Nyberg Gladstone‐UCSF Institute of Genomic Immunology, San Francisco, CA, USAandDivision of Hemato‐Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
Jenna Persson CRISPR Functional Genomics, Karolinska Institutet and SciLifeLab, Stockholm, Sweden
Martin Peterka Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Michelle J. Porritt Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Sivaprakash Ramalingam Genomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India
Steve Rees Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
Amélie Rezza genOway, Lyon, France
Saumyaa Saumyaa Translational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Molndal, Sweden
Bernhard Schmierer CRISPR Functional Genomics, Karolinska Institutet and SciLifeLab, Stockholm, Sweden
Niklas Selfjord Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Ning Sun Functional Genomics, R&D GlaxoSmithKline, Upper Providence, PA, USA
Saša Šviković Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Amir Taheri‐Ghahfarokhi Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Benjamin J.M. Taylor Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
Priya Thakur Genomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India
Pierre Theurey genOway, Lyon, France
Kader Thiam genOway, Lyon, France
Sandra Wimberger Discovery Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Part 1 Introduction to Drug Discovery and Genome Editing Methods
This part provides a historical prospective on developments in the genome editing field. Since CRISPR Cas is currently the method of choice, which in true sense has revolutionized genome editing, a separate chapter on the development of this technology is provided.
1 Genome Editing in Drug Discovery
Steve Rees
Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
1.1 Introduction
The last decade has seen the development of an unprecedented number of new technologies that are being applied to transform our understanding of disease and the subsequent success of drug discovery. The dramatic advances in DNA sequencing technology and the more recent advances in other‐omics technologies including transcriptomics, proteomics, and metabolomics are enabling the understanding of disease at the genetic and cellular level to identify new drug targets, and to identify new disease biomarkers to enable disease segmentation and patient stratification in the clinic. Advances in stem cell technology together with technologies that enable the creation of tissue organoids in the laboratory are allowing the creation of complex models of disease (Lancaster et al. 2013), which together with advances in imaging technology are enabling the drug discovery scientist to better understand the efficacy and safety of potential medicines in preclinical studies. The huge increases in computational power, together with advances in Artificial Intelligence and Machine Learning are allowing drug discovery scientists to extract greater knowledge from these large‐omics datasets, to improve the speed and quality of chemistry design and enable the design of improved clinical studies (Vamathevan et al. 2019). Perhaps, the most impactful of the many new technologies applied in drug discovery in the last decade has been the rapid adoption of CRISPR/Cas9 throughout the drug discovery pipeline to create engineered cellular and animal models of disease to enable the study of the role of new drug targets in disease, alongside the development of CRISPR as a medicine in it’s own right or as a key tool in the creation