title: 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.
authors.affiliation: Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Sadelain
mesh_terms: D000818:Animals; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005914:Globins / Q000235:genetics*; D006453:Hemoglobinopathies / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D013234:Stem Cells / Q000166:cytology*; D014161:Transduction, Genetic; D019076:Transgenes; D017086:beta-Thalassemia / Q000235:genetics
chemical_list: D005914:Globins