Gene therapy for inherited disorders of haematopoietic cells

Hematol J. 2004;5(2):103-11. doi: 10.1038/sj.thj.6200366.

Abstract

Over the last decade, the majority of inborn errors of haematopoiesis has been elucidated on a molecular level. For some of these diseases, gene transfer into transplantable cells offers new therapeutic perspectives. Improved retroviral or lentiviral techniques allow stable gene transfer in >10% of repopulating cells cultured in vitro. However, severe impediments are still encountered with respect to achieving sufficient and long-lasting transgene expression levels and appropriate numbers of transgenic cells in vivo. Improving the techniques for manipulation of stem cells in vitro, and the development of regimens promoting engraftment and selection of gene-modified cells are important areas of current research. Further activities address the level and persistence of transgene expression within individual cell clones, and the functional characteristics of progeny cells in vivo. Promises with respect to the potential impact of gene therapy for patients suffering from inherited disorders are often triggered by 'proof of concept' in preclinical disease models. However, recent observations of side effects related to random vector insertion or transgene expression indicate that even more careful quantitative and qualitative investigations of efficiency and toxicity may be needed for individual transgenes before approaching clinical trials.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Gene Expression / genetics
  • Gene Transfer Techniques
  • Genes, Reporter / genetics
  • Genetic Therapy* / methods
  • Genetic Vectors*
  • Hematologic Diseases / congenital
  • Hematologic Diseases / genetics*
  • Hematologic Diseases / pathology
  • Hematologic Diseases / therapy*
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Mice
  • Transgenes / genetics
  • Viruses