Hematopoietic Stem Cell Gene-Addition/Editing Therapy in Sickle Cell Disease

Cells

Anh Le¹  Naoya Uchida¹  Paula Germino-Watnick¹  Malikiya Hinds¹  Rebecca Chu¹  Xiong Liu¹ 

[1] Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institutes (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD 20892, USA;

关键词: hematopoietic stem cells;    transplantation;    gene therapy;    gene editing;    sickle cell disease;    in vivo gene therapy;   

DOI  :  10.3390/cells11111843

来源: DOAJ

【 摘 要 】

Autologous hematopoietic stem cell (HSC)-targeted gene therapy provides a one-time cure for various genetic diseases including sickle cell disease (SCD) and β-thalassemia. SCD is caused by a point mutation (20A > T) in the β-globin gene. Since SCD is the most common single-gene disorder, curing SCD is a primary goal in HSC gene therapy. β-thalassemia results from either the absence or the reduction of β-globin expression, and it can be cured using similar strategies. In HSC gene-addition therapy, patient CD34+ HSCs are genetically modified by adding a therapeutic β-globin gene with lentiviral transduction, followed by autologous transplantation. Alternatively, novel gene-editing therapies allow for the correction of the mutated β-globin gene, instead of addition. Furthermore, these diseases can be cured by γ-globin induction based on gene addition/editing in HSCs. In this review, we discuss HSC-targeted gene therapy in SCD with gene addition as well as gene editing.

【 授权许可】

Unknown