Main description:

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.

Contents:

1. Hematopoietic Stem Cells as Targets for Genetic Manipulation: Concepts and Practical Approaches; N.G. Testa, et al. 2. Bone Marrow Transplantation for Genetic Diseases; C.G. Stewart. 3. Retroviral Vectors; M. Collins, C. Porter. 4. Parvoviral Vectors for Human Hematopoietic Gene Therapy; A. Srivastava. 5. Nonviral Methods for Gene Transfer; A. Djeha, L.S. Lashford. 6. Prospects for Gene Therapy of Inherited Immunodeficiency; C. Casimir. 7. Gene Therapy for Lysosomal Disorders; L.J. Fairbairn, L.S. Lashford. 8. Genetic Approaches to Therapy for the Hemoglobinopathies; M. Antoniou, F. Grosveld. 9. Gene Marking and the Biology of Hematopoietic Cell Transfer in Human Clinical Trials; A.K. Stewart, et al. 10. Antisense Strategies to Leukemia; S.G. O'Brien. 11. Transfer of Drug Resistance Genes into Bone Marrow Stem and Progenitor Cells: Implications for Cancer Chemotherapy; J.A. Rafferty, L.J. Fairbairn. 12. HIV Gene Therapy Using Hairpin Ribozymes in Hematopoietic Stem/Progenitor Cells; Xinqiang Li, et al. 13. Molecular Immunotherapy by Gene Transfer; R.M. Diaz, R.G. Vile. 14. DNA-Based Immunization; H.L. Davis, et al.