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

Paula Germino-Watnick; Malikiya Hinds; Anh Le; Rebecca Chu; Xiong Liu; Naoya Uchida

doi:10.3390/cells11111843

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

Cells. 2022 Jun 4;11(11):1843. doi: 10.3390/cells11111843.

Authors

Paula Germino-Watnick¹, Malikiya Hinds¹, Anh Le¹, Rebecca Chu¹, Xiong Liu¹, Naoya Uchida^{1

2}

Affiliations

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.
² Division of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.

Abstract

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.

Keywords: gene editing; gene therapy; hematopoietic stem cells; in vivo gene therapy; sickle cell disease; transplantation.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Anemia, Sickle Cell* / genetics
Anemia, Sickle Cell* / metabolism
Anemia, Sickle Cell* / therapy
Gene Editing / methods
Genetic Therapy / methods
Hematopoietic Stem Cell Transplantation* / methods
Hematopoietic Stem Cells / metabolism
Humans
beta-Globins / genetics
beta-Thalassemia* / genetics
beta-Thalassemia* / metabolism
beta-Thalassemia* / therapy

Substances

beta-Globins

Grants and funding

This publication was supported by the Grant (New-2022-K1001) for International Joint Research Project of the Institute of Medical Science, the University of Tokyo, which is funded by Ministry of Education, Culture, Sports, Science and Technology in Japan.