Genome Editing in Drug Discovery

We felt a need for a book comprehensively covering these important aspects of genome editing in drug discovery and therapy. Such a book will be of very much interest for those performing genome editing in research institutes or applying genome editing to drug discovery projects at pharmaceutical industries. Such a book will also help students of molecular biology, biotechnology, biochemistry, and pharmaceutical sciences to better understand this very important technology and to exemplify how basic research on a bacterial immune system can have such a big impact in life sciences.

We would like to thank staff at Wiley, especially Jonathan Rose, who first proposed the idea of this book. We would like to thank all the authors who spent their precious time in making this book a reality. Each of the chapter is written by experts on the respective topic working in top pharmaceutical/biotechnology companies or academic institutes.

We would also like to thank colleagues and management at AstraZeneca, Mohammad Bohlooly, Steve Rees, Mike Snowden, and Mene Pangalos for supporting us and allowing us to devote our time for such an academic exercise.

Marcello Maresca and Sumit Deswal

Gothenburg, SwedenApril 2021

AAVAdeno-Associated VirusABEAdenosine Base EditorsADARAdenosine deaminases acting on RNAASOsAntisense oligonucleotidesCARChimeric Antigen ReceptorCas9CRISPR associated protein 9CBECytosine base editorsCRISPRClustered Regularly Interspaced Short Palindromic RepeatsCRISPRaCRISPR activationCRISPRiCRISPR interferencedCas9Dead Cas9DSBDouble strand DNA breakFACSFluorescence-activated cell sortingGEMMGenetically Engineered Mouse ModelHDRHomology Directed RepairiGEMInternational Genetically Engineered MachinesIPRIntellectual Property RightsLNPLipid Nano ParticlesNHEJNon-homologous end joiningPAMProtospacer adjacent motifspegRNAPrime editing guide RNARNAiRNA interferenceRNPRibonucleoproteinsgRNASingle guide RNAsiRNASmall interfering RNAshRNAShort hairpin RNATALENsTranscription activator-like effector nucleasesTGETherapeutic Genome EditingZFNsZinc finger nucleases

Pinar AkcakayaGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Nina AkrapDiscovery Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Lukas BadertscherGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Sangsu BaeDepartment of Chemistry and Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul, South Korea

Fiona M. BehanFunctional Genomics, R&D GlaxoSmithKline, Stevenage, UK

Nupur BhargavaGenomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India

Erik Oude BlenkeAdvanced Drug Delivery, Pharmaceutical Sciences, AstraZeneca R&D, Molndal, Sweden

Alessandro BonettiTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Molndal, Sweden

Rakesh Kantilal ChandodeGene Therapy, Functional and Mechanistic Safety, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Aaron T. ChengFunctional Genomics, R&D GlaxoSmithKline, Upper Providence, PA, USA

Yacine ChérifigenOway, Lyon, France

Matthew CoelhoWellcome Sanger Institute, Cambridge, UK

Sumit DeswalGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Ramy ElgendyTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Molndal, Sweden

Leire Escudero‐IbarzDiscovery Biology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK

Justin EyquemGladstone‐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 FraichardgenOway, Lyon, France

Davide GianniDiscovery Biology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK

Luke A. GilbertDepartments 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 GoswamiGenomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India

Antje GrotzGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Pragya GuptaGenomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India

Gue‐Ho HwangDepartment of Chemistry and Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul, South Korea

Shashank JaitlyGenomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India

Venkata R. KrishnamurthyAdvanced Drug Delivery, Pharmaceutical Sciences, AstraZeneca R&D, Boston, MA, USA

Songyuan LiGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Quinn LuNovel Human Genetics Research Unit, R&D GlaxoSmithKline, Upper Providence, PA, USA

Alexandra MadsenGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Franc MaliFaculty of Social Sciences, University of Ljubljana, Ljubljana, Slovenia

Klio MaratouFunctional Genomics, R&D GlaxoSmithKline, Stevenage, UK

Marcello MarescaGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Roberto NitschGene Therapy, Functional and Mechanistic Safety, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

William A. NybergGladstone‐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 PerssonCRISPR Functional Genomics, Karolinska Institutet and SciLifeLab, Stockholm, Sweden

Martin PeterkaGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Michelle J. PorrittGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Sivaprakash RamalingamGenomics and Molecular Medicine, CSIR‐Institute of Genomics and Integrative Biology, New Delhi, India

Steve ReesDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK

Amélie RezzagenOway, Lyon, France

Saumyaa SaumyaaTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Molndal, Sweden

Bernhard SchmiererCRISPR Functional Genomics, Karolinska Institutet and SciLifeLab, Stockholm, Sweden

Niklas SelfjordGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Ning SunFunctional Genomics, R&D GlaxoSmithKline, Upper Providence, PA, USA