2 Gene transfer into haemopoietic cells

Abstract

The therapeutic potential achievable by efficient transfer and expression of genes into haemopoietic stem cells (HSC) is enormous. In addition to inherited disorders such as haemoglobinopathies and lysosomal storage disorders, this technology can be applied to acquired disorders such as myelosuppression induced by anticancer chemotherapy or infection with human immunodeficiency virus (HIV). To date retroviral vectors are the most attractive modality for gene transfer into HSC. Unfortunately, the expectations of gene therapy are more advanced than the methodology needed to fulfil the goals. In this chapter, the current concepts and limitations in the genetic manipulation of haemopoietic cells are presented. Overcoming these limitations requires not only improvement in isolation and expansion of HSC that contribute to long-term repopulation, but also development of better retroviral transfer systems. Current restrictions occur at various levels in the viral transfer process, including efficient cell entry, regulated expression levels, and sustained expression. The analysis of retroviral mutants has proven to be a successful approach to developing effective retroviral vectors for HSC gene therapy.