Vectors for Gene Therapy: Strategies for Making Gene Therapy Work

  • D. E. Onions
Part of the Developments in Hematology and Immunology book series (DIHI, volume 30)


In the last 5 years gene therapy has emerged from laboratory experimentation to clinical reality with the prospect of treating monogenic deficiency diseases, some neoplasias and perhaps ameliorating the effects of persistent virus infections like HIV. It is an axiom in gene therapy that the aim is to deliver a therapeutic gene to as many of the target cells as possible and to ensure the expression of that gene for an extended period. Consequently, gene therapy using haemopoietic stem cell targets is an attractive proposition as transduction of a CD34+ stem cell can lead to the establishment of expression in many progeny cells. However, the delivery of genes and the maintenance of expression in many progeny cells. However, the delivery of genes and the maintenance of expression remain formidable problems. Viral vectors offer the most effective method for gene delivery to haemopoietic cells and out of the first 81 gene therapy applications approved in the United States 63 used retrovirus vectors. While other vectors like adenovirus vectors or adeno-associatedvirus (AAV) vectors may also have a role in transduction of bone marrow cells the retroviruses have a number of advantages. Like AAV they are able to integrate DNA copies of their genomes or proviruses into chromosomal DNA without the complex rearrangements associated with other transduction processes. Nevertheless there are disadvantage with these vectors, in particular there are concerns over their safety and limitations on the insert size that they can carry. Eventually synthetic systems utilising targeting and integration systems derived from viruses may become feasible but in the medium term retrovirus and AAV vectors offer the most useful approach to gene therapy through haemopoietic stem cells.


Gene Therapy Packaging Cell Line Haemopoietic Stem Cell Replication Competent Virus Amphotropic Murine Leukaemia Virus 
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© Springer Science+Business Media Dordrecht 1995

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  • D. E. Onions

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