Genome Editing in Drug Discovery. Группа авторов

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