Stem cell gene therapy for the beta-chain hemoglobinopathies. Problems and progress.

ABSTRACT

Virus vectors hold great promise for the stem cell gene therapy of beta-chain hemoglobinopathies. However, conventional vectors suffer from low gene transfer rates, low expression levels, and inconsistent or short-lived expression in vivo. In this review we summarize the current status of vector systems for the transduction of hematopoietic stem cells, including the development of novel vector systems and methods for selection of transduced stem cells in vivo. We also summarize efforts to achieve therapeutic expression levels of transferred globin genes with retrovirus vectors, including the manipulation of transcription cassettes, the use of globin gene enhancers, and advances in the use of chromatin insulators for improving the frequency of gene expression following hematopoietic stem cell transduction.