Description
Springer Blood Cell Biochemistry Hematopoiesis and Gene Therapy 1st Editon 2012 Softbound by Leslie J. Fairbairn, Nydia G. Testa
Since the first concepts of gene therapy were formulated, the hemopoietic system has been considered the most natural first target tissue for genetic manipulation. The reasons for this include the fact that a very large number of inherited disorders (including some of the most common disorders, such as the hemoglobinopathies) are disorders of the hemopoietic system, and the large amount of experience in hematopoietic transplantation biology. The consequence of this resulted in the first clinical trial of gene therapy in 1989, where two children suffering from severe combined immune deficiency (ADA-SCID) were transplanted with T-cells express ing adenosine deaminase (the defective enzyme in patients with this disorder). The partial success of this treatment was perhaps responsible for undue optimism among those proposing other gene therapy treatments within the hematopoietic system, and it has since become clear that there are a number of technical and biological difficulties to overcome before hematopoietic gene therapy becomes a mainstream therapeutic strategy. The chapters in this book evaluate the need for gene therapy in the hematopoietic system, discuss how efficient gene transfer and expression can be achieved in the target cells, highlight areas of difficulty to be addressed, and examine a number of potential applications of the gene therapy approach. The book begins with a chapter by Testa and colleagues, discussing the various sources of hematopoietic cells for both transplantation and gene therapy. 1 Hemopoietic Stem Cells as Targets for Genetic Manipulation: Concepts and Practical Approaches.- 1. How Many Stem Cells Do We Need?.- 2. Selection and Identification by Phenotype and Function.- 3. Sources of Primitive Hematopoietic Cells.- 4. How Can We Maximize the Number of Target Cells?.- 5. Concluding Comments.- 6. References.- 2 Bone Marrow Transplantation for Genetic Diseases.- 1. Introduction.- 2. General Principles of BMT.- 3. The Bone Marrow Transplantation Process.- 4. Complications of BMT.- 5. Results of BMT.- 6. Future Directions.- 7. References.- 3 Retroviral Vectors.- 1. Why Retroviruses?.- 2. The Basic Vector.- 3. The Packaging Cell.- 4. References.- 4 Parvoviral Vectors for Human Hematopoietic Gene Therapy.- 1. Introduction.- 2. Life Cycle of Human Parvoviruses.- 3. Recombinant Parvoviral Vectors.- 4. Parvovirus-Mediated Transduction and Expression of Genes.- 5. Advantages and Disadvantages of Parvovirus Vectors.- 6. Summary and Conclusions.- 7. Future Prospects.- 8. References.- 5 Nonviral Methods for Gene Transfer.- 1. Introduction.- 2. Plasmid DNA-Based Methods.- 3. Artificial Self-Assembling Systems.- 4. References.- 6 Prospects for Gene Therapy of Inherited Immunodeficiency.- 1. Introduction to Gene Therapy.- 2. Immunodeficiency Disorders.- 3. Vector Systems and Their Suitability for Gene Therapy of Immunodeficiency.- 4. Gene Therapy for Immunodeficiency Disorders.- 5. Conclusion.- 6. References.- 7 Gene Therapy for Lysosomal Disorders.- 1. Defining a Population of Patients Suitable for Treatment.- 2. Gene Therapy.- 3. Targeting the Brain.- 4. Conclusions.- 5. References.- 8 Genetic Approaches to Therapy for the Hemoglobinopathies.- 1. Introduction.- 2. Current Therapies for ?-Thalassaemia.- 3. Current Therapies for Sickle Cell Disease.- 4. Regulation of Gene Expression from the Human ?-Globin Locus.- 5. Pharmaceutical Activation of Fetal ?-Globin Gene Expression in the Adult.- 6. Gene Therapy.- 7. Summary and Future Prospects.- 8. References.- 9 Gene Marking and the Biology of Hematopoietic Cell Transfer in Human Clinical Trials.- 1. Introduction.- 2. Gene Marking and Cancer Biology.- 3. Retroviral Marking of Tumor-Infiltrating Lymphocytes.- 4. Clinical Trials of Stem Cell Gene Marking.- 5. Clinical Trial Design.- 6. Retroviral Marking of Malignant Cells.- 7. Clinical Trial Results.- 8. Hematopoiesis and Gene Marking.- 9. Genetically Marked Relapse.- 10. Retroviral Gene Marking and Purging Efficacy.- 11. Implications of Gene Marking Results in Clinical Practice.- 12. In Vitro Strategies to Improve Hematopoietic Stem Cell Targeting.- 13. Future Directions.- 14. Summary.- 15. References.- 10 Antisense Strategies to Leukemia.- 1. Introduction.- 2. Antisense and Ribozymal Design and Mechanisms of Action.- 3. Controls, Experimental Systems, and Difficulties in Interpretation.- 4. Antisense and Ribozymes in Experimental Hematology.- 5. Clinical Trials in Hematology.- 6. Future Prospects.- 7. References.- 11 Transfer of Drug Resistance Genes into Bone Marrow Stem and Progenitor Cells: Implications for Cancer Chemotherapy.- 1. Introduction.- 2. Current Strategies for Hematopoietic Support during Chemotherapy.- 3. Gene Transfer, Expression, and Stem Cell Protection.- 4. Further Considerations.- 5. Concluding Remarks.- 6. References.- 12 HIV Gene Therapy Using Hairpin Ribozymes in Hematopoietic Stem/Progenitor Cells.- 1. Ribozyme for Gene Therapy of AIDS.- 2. Gene Therapy Using Hematopoietic Stem/Progenitor Cells.- 3. Transduction of Stem/Progenitor Cells Using Ribozymal Constructs.- 4. Toward Clinical Trials.- 5. References.- 13 Molecular Immunotherapy by Gene Transfer.- 1. Introduction.- 2. Are Tumors Antigenic?.- 3. Antigen Presentation Pathways.- 4. Immunotherapy by Gene Transfer.- 5. Aims, Goals, and Targets for Gene Transfer in Immunotherapy.- 6. Unification of Diverse Results from Gene Transfer Studies.- 7. R