Genome Editing in Cardiovascular and Metabolic Diseases

Contents
Contributors
Part I: Overview
An Overview of Genome Editing in Cardiovascular and Metabolic Diseases
1 Genome-Editing Technologies
1.1 Nuclease Editing
1.2 Base Editing
1.3 Epigenome Editing
1.4 Other Types of Editing
2 Disease Modeling and Diagnostics
3 Therapeutic Genome Editing
4 Outlook
References
Part II: Bioinformatics
Online Databases of Genome Editing in Cardiovascular and Metabolic Diseases
1 Cardiovascular and Metabolic Disease Genetic Basis
2 Significance of Genome Editing in Cardiovascular and Metabolic Diseases
3 Lung Genetic Disorders and Therapeutic Options
4 History and Genome Editing at Present
5 How to Perform a Genome Editing Experiment Nowadays (CRISPR-Cas)
5.1 Molecular Mechanism and Components of the CRISPR-Cas System
6 How to Prepare a CRISPR-Cas Experiment
7 Different Types of CRISPR-Cas-Based System
8 Off-Target Effect, Predictive Tools, and Strategies to Avoid Them
9 Guide RNA Designing and Available Online Tools and Databases
10 Transfection Mechanisms
11 Cardiovascular and Metabolic Disease Genome Editing in the Field
12 Experiments Using CRISPR-Cas9
12.1 PRKAG2 Cardiac Syndrome
12.2 MYH7 Dysfunction
13 Experiments Using TALENs
13.1 PLN-Associated Hereditary Heart Failure
13.2 Obesity and LepR
14 Experiments Using ZFN
14.1 FBN1 and Marfan Syndrome
References
Part III: Genome Editing in Cardiovascular Disease
Genome Editing and Cardiac Regeneration
1 Background
2 Scope of Cardiac Regeneration
2.1 Understanding Cardiac Regeneration from Animal Models
2.2 Developing Approaches for Cardiac Regeneration
3 Pathways and Regulators of Cardiac Regeneration
3.1 Hippo Signaling Pathway
3.2 Wnt Signaling Pathway
3.3 PI3K-AKT Signaling Pathway
4 Approaches to Cardiac Regeneration
4.1 Genome Editing of Endogenous Cells to Initiate Cardiac Repair
4.1.1 In Situ Promotion of Proliferation and Cell Cycle Re-entry
4.1.2 In Vivo Trans-differentiation of Cardiac Fibroblasts
4.2 Transplantation of Exogenous Cells
5 Perspective
References
Genome Editing and Myocardial Development
1 Overview
2 Cardiac Development
2.1 Early Development and Cardiac Crescent
2.2 Cardiac Looping
2.3 Atrium, Sino Atrial Node, and Atrial Ventricular Node Development
2.4 Ventricular Development
2.5 Atrioventricular Valve Development
2.6 Outflow Track Development
2.7 Conductance System
3 Genetic Archetypes in Cardiac Development
4 Genetic Archetypes for Syndromic Congenital Heart Defects
5 Genetic Archetypes of Nonsyndromic Isolated Congenital Heart Defects
6 Genetic Archetypes for Left-Right Patterning
7 Genetic Archetypes of Inherited Arrhythmias
7.1 Long QT Syndromes
7.2 Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
7.3 Brugada Syndromes (BrS)
7.4 Short QT Syndrome (SQTS)
8 Genetic Archetypes of Inherited Cardiomyopathy
8.1 Dilated Cardiomyopathy (DCM)
8.2 Hypertrophic Cardiomyopathy (HCM)
8.3 Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
8.4 Restrictive Cardiomyopathy (RCM)
8.5 Left Ventricular Non-compaction Cardiomyopathy
8.6 Cardiomyopathy in Other Disorders
9 Genome Editing in Modeling Inheritable Heart Diseases in Model Organisms
10 Other Considerations
11 Conclusions
References
Genome Editing and Heart Failure
1 Introduction
2 Pathophysiology of Heart Failure
3 Management of Heart Failure with a Reduced Ejection Fraction
4 Management of Heart Failure with a Preserved Ejection Fraction
5 The Genetic Architecture of Heart Failure
6 Tools for Genome Editing
7 Genome Editing in Heart Failure
8 Using Genome Editing to Create In Vitro and In Vivo Disease Models of Heart Failure
9 Genome Editing for Therapy of Heart Failure
10 Conclusions
References
Genome Editing and Pathological Cardiac Hypertrophy
1 Introduction
2 Genetic Backgrounds of Cardiomyopathies
2.1 HCM and DCM
2.2 Arrhythmogenic Right Ventricular Cardiomyopathy
2.3 Restrictive Cardiomyopathy
2.4 Left Ventricular Noncompaction Cardiomyopathy (LVNC)
3 Genome Editing in Cell Models of Cardiac Disease
4 Genome Editing in Animal Models
5 Germline and Somatic Genome as a Therapeutic Implication and Ethical Problems
6 Hypertrophic Cardiomyopathy and Genome Editing
7 Duchenne Muscular Dystrophy and Genome Editing
8 Transthyretin Cardiac Amyloidosis
9 Long QT Syndrome
10 Future Directions in CRISPR and Cardiomyopathy Treatment
11 Advances in Nonviral Delivery System
12 Conclusions
References
Genome Editing and Diabetic Cardiomyopathy
1 Introduction
2 Diabetic Cardiomyopathy
3 Genetic Editing
4 Advancement in Genetic Editing Technology
5 Genetic Editing in Diabetic Cardiomyopathy
6 Future Direction
References
Genome Editing and Inherited Cardiac Arrhythmias
1 Introduction
2 Long QT Syndrome
3 Brugada Syndrome
3.1 Catecholaminergic Polymorphic Ventricular Tachycardia
4 Short QT Syndrome
5 Summary and Future Perspectives
References
Genome Editing and Atrial Fibrillation
1 Background
2 Genome Editing and Atrial Fibrillation
3 Atrial Fibrillation Substrate and Modifiable Electrical Targets
3.1 Ion Channels
3.2 Gap Junctions
3.3 Parasympathetic Signaling
4 Atrial Fibrillation Substrate and Modifiable Structural Aspects
4.1 Fibrosis
4.2 Apoptosis
5 Oxidative Stress and Modifiable Structural and Electrical Aspects
5.1 ROS Generation and NADPH Oxidase
5.2 Oxidized Calmodulin-Dependent Protein Kinase II (oxCAMKII)
6 Conclusions
References
Genome Editing in Dyslipidemia and Atherosclerosis
1 Dyslipidemia and Atherosclerosis
2 Current Therapies of Dyslipidemia and Atherosclerosis
2.1 From Traditional Pharmacology to Targeted Therapy
2.2 Nucleic Acid-Based Therapy
3 Genome Editing
3.1 Evolution of Genome Editing Technology
3.2 In Vivo Delivery of Genome Editing Systems
4 Genome Editing in Dyslipidemia and Atherosclerosis
4.1 Genome Editing: A Driving Force for Dyslipidemia and Atherosclerosis Research
4.2 Preclinical Investigation of Genome Editing for Dyslipidemia and Atherosclerosis
4.3 Further Target Discovery for Dyslipidemia and Atherosclerosis
4.3.1 Gene and Variant Targets Inspired by Human Knockout
4.3.2 Candidate Genes and Variants from Large-Scale Genetic Studies
4.3.3 Driver Genes and Variants of Systems Genetic Studies
5 Concluding Remarks and Future Perspectives
References
Genome Editing to Abrogate Muscle Atrophy
1 Background
2 Muscle Atrophy
2.1 Aging
2.2 Nerve Injury
2.3 Immobilization
2.4 Fasting
2.5 Chronic Heart Failure
2.6 Cachexia
3 Protein Synthesis and Degradation in Muscle Atrophy
3.1 The Ubiquitin-Proteasome System
3.2 The Autophagy-Lysosome System
4 Molecular Pathways Underlying Muscle Atrophy
4.1 IGF1-Akt-FoxO Pathway
4.2 NF-kappaB Pathway
4.3 Myostatin Pathway
4.4 beta2-Adrenoceptor Pathway
5 Genome Editing in Muscle Atrophy
5.1 Genome Editing
5.1.1 Meganuclease
5.1.2 Zinc Finger Nuclease (ZFN)
5.1.3 Transcriptional Activation-Like Effector Nuclease (TALEN)
5.1.4 CRISPR/Cas9 System
5.2 Application of Genome Editing in Muscle Atrophy
6 Developing Approaches for Muscle Atrophy
References
Part IV: Genome Editing in Metabolic Diseases
Genome Editing and Obesity
1 Introduction
2 The Genetics Underlying Obesity
2.1 Monogenic Obesity
2.2 Polygenic Obesity
3 Currently Available Obesity Treatments
3.1 Dietary Changes, Exercise and Behaviour Therapy
3.2 Prescription Weight-Loss Medication
3.3 Metabolic Surgery
4 Latest Strategies for Obesity Treatment
4.1 Genome Editing Tools for Therapeutics in Obesity
5 Conclusions
References
Genome Editing and Fatty Liver
1 Background
1.1 Pathophysiology of Alcoholic Liver Disease
1.2 Pathophysiology of Nonalcoholic Fatty Liver Disease
2 Genetic Variants and Fatty Liver Disease
2.1 Candidate Gene Studies
2.2 GWAS Findings
2.3 Transmembrane 6 Superfamily 2 (TM6SF2)
2.4 Glucokinase Regulator (GCKR)
2.5 Patatin-Like Phospholipase Domain-Containing Protein 3 (PNPLA3)
2.6 Membrane-Bound O-acetyltransferase Domain-Containing 7 (MBOAT7)
2.7 Heme Oxygenase (HMOX1)
2.8 Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase (ALDH)
3 Gene Editing Models for Fatty Liver Disease
3.1 CRISPR/Cas9: A Genome Editing Tool
3.2 Mechanism of CRISPR/Cas9 Genome Editing
3.3 CRISPR/Cas9-Mediated Nonalcoholic Fatty Liver Disease (NAFLD) Models
3.3.1 Transmembrane 6 Superfamily 2 (TM6SF2)-Targeted Fatty Liver Disease Models
3.3.2 PNPLA3-Targeted Models
3.3.3 Miscellaneous Models
4 ``Good Fit´´ Genome Editing Tool Selection for ALD and NAFLD Variant Replication
4.1 Cutting-Edge Cas9 Variants
4.1.1 Base Editor for Fatty Liver Disease Genome Variants
4.1.2 Prime Editor for ALD and NAFLD Genome Variants
4.2 Gene Delivery Methods for Refining Efficacy of Gene Editing Process
4.2.1 Nonviral Delivery Methods
4.2.2 Viral Delivery Methods
5 Discussion
6 Future Implications
7 Conclusions
References
Genomic Editing and Diabetes
1 Background
2 Risk Factors
2.1 Interplay of Nongenetic Risk Factors
2.2 Genetics of Diabetes
2.2.1 Transcription Factor 7-Like 2 (TCF7L2) Gene
2.2.2 ATP Binding Cassette Subfamily C Member 8 (ABCC8)
2.2.3 Solute Carrier Family 2 Member 2 (SLC2A2)
2.2.4 Calcium-Activated Neutral Proteinase 10 (CAPN10)
3 Overview of Current Diabetes Management
3.1 Diabetes Mellitus Type I
3.2 Diabetes Mellitus Type II
4 Genomic Editing
4.1 Genetic Modification of Stem Cells
4.2 CRISPR/Cas9 Gene Editing
4.3 MicroRNAs
4.4 Long Noncoding RNA
5 Conclusion
References
Genome Editing and Protein Energy Malnutrition
1 Background
2 Marasmus
3 Kwashiorkor
4 Strategic Regulations of Protein-Energy Malnutrition
5 Protein Malnutrition and Genetic Modification
6 Genetic Engineering: An Opportunity to Control Protein-Energy Malnutrition
7 Strategies to Improve Plants´ Nutritional Status Using Genetic Engineering
8 Plants, Crops, and Vegetable Nutrition
9 Animal Nutrition
References
Part V: Therapeutic Implications
Gene Therapy and Cardiovascular Diseases
1 Background
2 History of Gene Therapy
3 Material and Approach of Gene Therapy
4 CRISPR-Cas-Mediated Gene Editing
5 Nonviral-Mediated Gene Therapy Methods
6 siRNA and RNA Inhibitors
7 Nucleic Acid Drugs
8 Viral-Based Approach for Gene Therapy
9 Gene Therapy in CVDs
10 Future Perspectives of Gene Therapy in CVDs
11 AAV Engineering for Heart-Specific Therapy
12 Successful Viral-Based Gene Therapy in Clinical Trials
13 Novel Therapeutic Target Genes
14 Conclusion
References
Therapeutics in Metabolic Diseases
1 Background
2 The Lifestyle Changes as Treatment for Metabolic Diseases
2.1 Physical Activity and Exercise
2.2 Diet
2.3 Alcohol and Smoking Cessation
2.4 Losing Weight
2.5 Stress Control
3 The Pharmacotherapy of Metabolic Diseases
3.1 Pharmacotherapy of Dyslipidemia
3.2 Pharmacotherapy of Obesity
3.3 Pharmacotherapy of Diabetes Mellitus
3.4 Pharmacotherapy of Hypertension
3.5 Therapeutics for Other Rare Metabolic Diseases
4 Gene Therapy
5 Natural or Phytomedicines
6 Other Treatments
7 Perspective
References
Gene Editing and Human iPSCs in Cardiovascular and Metabolic Diseases
1 Background
2 CRISPR/Cas9
3 CRISPR Cas9 and Cardiometabolic Diseases: Lessons from Animal Models
4 Human iPSC and Their Potential for the Modeling of Cardiometabolic Diseases
5 Gene Editing in Human iPSC
6 CRISPR Cas9 and Gene Editing in Human iPSC
6.1 CRISPR Cas9 and Gene Editing in Human iPSC: Impact on Cardiovascular Research and Therapy
6.2 CRISPR Cas9 and Gene Editing in Human iPSC: Impact on Metabolic Disease Research and Therapy
7 Gene Editing, iPSC, and Clinical Trials
8 Limitations and Challenges of iPSC and Editing Technologies
9 Perspective
References
Part VI: Future Prospects
Prospective Advances in Genome Editing Investigation
1 Advances in Genome Editing Investigation
2 CRISPR/Cas9 Editing Properties and Limits
3 Advances in Genome Editing Investigation in Cardiovascular Disease Applications
4 Advances in Genome Editing Investigation in Metabolic Disease Application
5 Advances in Genome Editing Investigation in Inflammatory Disease, Oral Diseases,Malformations and Cancer
6 Future Directions
References
Enabling Precision Medicine with CRISPR-Cas Genome Editing Technology: A Translational Perspective
1 Introduction
2 CRISPR-Cas Toolbox for Genome Manipulation
2.1 Cas9 Nuclease
2.2 Cas12 Nucleases
2.3 Cas13 Nucleases
3 CRISPR-Cas Payloads and Delivery
3.1 CRISPR-Cas Payloads
3.2 CRISPR-Cas Delivery Vehicles
4 CRISPR-Cas: Challenges for Clinical Implementation
4.1 Off-Target Mutagenesis
4.2 Genome Editing Efficiency
4.3 Immunogenicity
4.4 Preclinical Studies
5 CRISPR-Cas in the Clinic
5.1 Ex Vivo Strategies
5.2 In vivo Strategies
6 Conclusion
References