title: Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.
abstract: Effective medical management for sickle cell disease (SCD) remains elusive. As a prevalent and severe monogenic disorder, SCD has been long considered a logical candidate for gene therapy. Significant progress has been made in moving toward this goal. These efforts have provided substantial insight into the natural regulation of the globin genes and illuminated challenges for genetic manipulation of the hematopoietic system. The initial γ-retroviral vectors, next-generation lentiviral vectors, and novel genome engineering and gene regulation approaches each share the goal of preventing erythrocyte sickling. After years of preclinical studies, several clinical trials for SCD gene therapies are now open. This review focuses on progress made toward achieving gene therapy, the current state of the field, consideration of factors that may determine clinical success, and prospects for future development.
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA; and.
authors.forename: Megan D
authors.identifier: http://orcid.org/0000-0002-5011-9582
authors.initials: MD
authors.lastname: Hoban
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA; and Howard Hughes Medical Institute, Boston, MA.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA; and.
authors.forename: Daniel E
authors.identifier: http://orcid.org/0000-0001-5076-7945
authors.initials: DE
authors.lastname: Bauer
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics* / Q000628:therapy*; D002986:Clinical Trials as Topic; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D015894:Genome, Human; D006801:Humans