Marcello Maresca - Genome Editing in Drug Discovery

1. Chapter 4
2. Chapter 5
3. Chapter 6
4. Chapter 7
5. Chapter 8
6. Chapter 9
7. Chapter 11
8. Chapter 12
9. Chapter 13
10. Chapter 15
11. Chapter 16
12. Chapter 17
13. Chapter 18
14. Chapter 20

1. Chapter 2
2. Chapter 3
3. Chapter 4
4. Chapter 6
5. Chapter 7
6. Chapter 8
7. Chapter 9
8. Chapter 10
9. Chapter 11
10. Chapter 12
11. Chapter 13
12. Chapter 14
13. Chapter 15
14. Chapter 16
15. Chapter 17
16. Chapter 18
17. Chapter 19
18. Chapter 20
19. Chapter 22

Edited by

Marcello Maresca

AstraZeneca, BioPharmaceuticals R&D

Mlndal, Sweden

Sumit Deswal

AstraZeneca, BioPharmaceuticals R&D

Mlndal, Sweden

This edition first published 2022.
2022 John Wiley & Sons, Inc.

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The right of Marcello Maresca and Sumit Deswal to be identified as the authors of the editorial material in this work has been asserted in accordance with law.

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Library of Congress CataloginginPublication Data

Names: Maresca, Marcello, editor. | Deswal, Sumit, editor.
Title: Genome editing in drug discovery / Marcello Maresca, AstraZeneca, BioPharmaceuticals R&D, Mlndal, Sweden, Sumit Deswal, AstraZeneca, BioPharmaceuticals R&D, Mlndal, Sweden.
Description: First edition. | Hoboken, NJ : Wiley, 2022. | Includes index.
Identifiers: LCCN 2021025952 (print) | LCCN 2021025953 (ebook) | ISBN 9781119671343 (hardback) | ISBN 9781119671381 (adobe pdf) | ISBN 9781119671398 (epub)
Subjects: LCSH: Drug development. | Genetic engineering.
Classification: LCC RM301.25 .G46 2022 (print) | LCC RM301.25 (ebook) | DDC 615.1/9dc23
LC record available at https://lccn.loc.gov/2021025952
LC ebook record available at https://lccn.loc.gov/2021025953

Cover image: Yurchanka Siarhei/Shutterstock
Cover design by Wiley

The development of CRISPRCas9 for genome engineering has revolutionized the field of genome editing. Many of the cell types and animal models previously very challenging to genetic engineering, can now be engineered with high efficiency and precision using CRISPRCas9derived tools. This has led to the development of many novel disease models helping scientists to better understand disease biology as well as providing opportunity to test novel therapeutics. By performing largescale functional genomics screens with CRISPRCas9, it is now possible to identify and validate drug targets at a much faster rate and better precision. By assessing gene function comprehensively at large scale and in relevant cell type in early stages, candidate attrition rate is reduced. Genome editing is now part of almost every step in the early part of drug discovery pipeline, from target identification and its validation to mechanistic studies in relevant disease models. In addition, genome editing is used as a promising platform for gene therapy and molecular diagnostics.

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 Next page