Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease

Blood. 2016 Feb 18;127(7):839-48. doi: 10.1182/blood-2015-09-618587. Epub 2016 Jan 12.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia, Sickle Cell / genetics*
  • Anemia, Sickle Cell / therapy*
  • Clinical Trials as Topic
  • Gene Expression Regulation
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use
  • Genome, Human
  • Humans