Genome Editing in Drug Discovery. Группа авторов

8.2 Pooled CRISPR‐Cas Screens 8.3 Reagents 8.4 Library Transduction, Maintenance, and Next‐Generation Sequencing 8.5 Screen to Target Selection 8.6 In vivo CRISPR Screens 8.7 Advanced Functional Genomics Screens 8.8 Selected Applications of Pooled CRISPR‐Cas Screens 8.9 Outlook References 9 Functional Genomics 9.1 Introduction 9.2 Array Format Technologies 9.3 CRISPR Reagent Delivery Systems 9.4 PreClinical Models in Array Screening 9.5 Phenotypic Screening Readouts 9.6 Bioinformatic Pipeline References 10 Applications of CRISPRi and CRISPRa in Drug Discovery 10.1 Introduction 10.2 Retooling CRISPR to Repress Gene Expression in Human Cells 10.3 Retooling CRISPR to Activate Gene Expression in Human Cells 10.4 Multiplexed CRISPRi/a Genetic Perturbations 10.5 CRISPRi/a Functional Genomics as a Discovery Modality 10.6 Identifying Gene Targets for the Treatment of Disease Using CRISPRi/a 10.7 Identification of Mechanisms of Response and Resistance to Drugs by CRISPRi and CRISPRa 10.8 CRISPRi/a Genetic Interaction Mapping for Drug Discovery 10.9 Conclusion References 11 Sequence Diversification Screens with CRISPR‐Cas9‐Guided Base Editors 11.1 Introduction 11.2 CRISPR as a Genetic Screening Method 11.3 Conventional Genetic Loss‐ and Gain‐of‐Function Screens Using CRISPR 11.4 Sequence Diversification Screens Using CRISPR Base Editing 11.5 Applications for Base‐Editor Screening 11.6 Conclusion Acknowledgements References 12 Single‐Cell Transcriptomics and Epigenomics for CRISPR‐Mediated Perturbation Studies 12.1 Introduction 12.2 CRISPR‐Based Genetic Screens with Single‐Cell Transcriptomics Readout 12.3 CRISPR‐Based Genetic Screens with Single‐Cell Epigenomics Readout 12.4 Future Perspectives Acknowledgments References

      10  Part 4: Therapeutic Genome Editing 13 DNA Repair Pathways in the Context of Therapeutic Genome Editing 13.1 Reprogrammable Nucleases 13.2 DNA Double‐Strand Break Repair Pathways 13.3 Strategies to Improve Knock‐In (KI) 13.4 Genome Editing in Clinical Trials 13.5 Major Safety Considerations in TGE Clinical Trials 13.6 Conclusion References 14 DNA Base Editing Strategies for Genome Editing 14.1 Introduction 14.2 Base Editor Architectures 14.3 Safety Considerations for Base Editing 14.4 Improving Precision, Efficiency, and Specificity 14.5 Prime Editing and Base Editing 14.6 Choosing the Right Editor 14.7 Therapeutic Uses of Base Editors 14.8 Conclusions References 15 RNA Base Editing Technologies for Gene Therapy 15.1 Introduction 15.2 RNA Editing Technologies 15.3 Potential Clinical Applications of RNA Editing 15.4 Challenges and Opportunities 15.5 Conclusions References 16 Genome Editing Applications in Cancer T Cell Therapy 16.1 Introduction 16.2 CAR T Cells