Globin gene transfer for the treatment of severe hemoglobinopathies: a paradigm for stem cell-based gene therapy

Abstract

The prospect of treating blood disorders with genetically modified stem cells is highly promising. This therapeutic approach, however, raises a number of fundamental biological questions, spanning several research fields. Further investigation is required to better understand how to isolate and efficiently transduce hematopoietic stem cells (HSCs), while preserving optimal homing and self-renewing properties; how to design safe vectors permitting controlled expression of the transgene products; and how to promote host repopulation by engrafted HSCs. This article addresses basic issues in stem cell-based gene therapy from the perspective of regulating transgene expression, taking globin gene transfer for the treatment of severe hemoglobinopathies as a paradigm.