Nonsense Mutation Correction in Human Diseases

Nonsense Mutation Correction in Human Diseases: An Approach for Targeted Medicine provides an introduction on genetic diseases, discusses the prevalence of nonsense mutations, the consequences of a nonsense mutation for the expression of the mutant gene, and the presentation of the nonsense-mediated mRNA decay (NMD).

It presents the mechanism of action and rationale associated with each strategy to correct nonsense mutations with the results of clinical trials to further support this basis. In addition, the book shows how it may be possible to combine several of these strategies to ultimately improve the efficiency of correction, also suggesting the future goals and objectives to improve treatment modalities in this evolving sphere of personalized medicine.

• Features basic biological and clinical constructs that inform the application of genomic data to clinical decision-making
• Includes theories and methods that can be used to link bio-molecular and clinical phenotypes so as to enable integrative hypothesis discovery, testing, and downstream evidence-based practice
• Provides design patterns and use cases that contextualize the clinical decision-making and evidence-based practice relative to real world requirements and stakeholders

Investigators at all levels in biomedicine, molecular biology and biochemistry; graduate and postdoc students in biomed, biology, and life science programs, clinicians interested in learning the underpinnings of personalized medicine

• About the Authors
• Acknowledgments
• Chapter 1: General Aspects Related to Nonsense Mutations
  • Abstract
  • 1. Premature termination codon, nonsense mutation, and consequences on gene expression
  • 2. Pre-mRNA splicing mechanism
  • 3. Nonsense-mediated mRNA decay (NMD) mechanism
  • 4. Correction of nonsense mutations, a case of targeted therapy
• Chapter 2: Pathologies Susceptible to be Targeted for Nonsense Mutation Therapies
  • Abstract
  • 1. Rare diseases
  • 2. Frequent diseases
• Chapter 3: Strategies to Correct Nonsense Mutations
  • Abstract
  • 1. The exon skipping
  • 2. Trans-splicing
  • 3. PTC-readthrough
  • 4. NMD inhibition
  • 5. Pseudouridylation at the PTC
  • 6. Gene therapy
  • 7. Cell therapy
  • 8. Genome editing
  • 9. Combinatory approaches to improve nonsense mutation therapies
• Chapter 4: Conclusions
  • Abstract
  • 1. Summary on the different strategies and their results
  • 2. Personalized/targeted medicine versus traditional medicine
  • 3. Limitations on nonsense mutation therapies and future considerations
• Glossary
• Subject Index