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Hematopoietic Stem Cell-Targeted Gene Therapy Using Lentiviral Vectors
Naoya Uchida
Cellular and Molecular Therapeutics Branch (CMTB), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)
Gene therapy targeting hematopoietic stem cells (HSCs) is a promising treatment for a variety of genetic disorders, including immunodeficiency, hemoglobinopathies, congenital cytopenia, and metabolic diseases. HSCs can reconstitute peripheral blood throughout life due to their capacity for self-renewal and their hematopoietic multipotency. This makes it possible to cure genetic diseases for an entire lifetime by replacing or repairing pathogenic mutations/deletions in HSCs. Autologous HSC-targeted gene therapies entailing lentiviral gene addition as well as gene editing are currently under development. These can be widely applied to most patients, as there is no requirement for a suitable donor. Current gene addition/editing therapies are based on harvesting the patient's CD34+ HSCs, performing gene modification ex vivo, and then transplanting the modified HSCs back into the patient. The efficacy of ex vivo lentiviral HSC gene therapy has been proved in recent trials; however, the ex vivo process requires a GMP-level cell processing center and is expensive, which limits its global application. It is therefore crucial to develop in vivo HSC gene therapies, in which a therapeutic gene or gene editing tools can be delivered directly into bone marrow HSCs via systemic administration without ex vivo culture. This manuscript presents an overview of the current HSCtargeted gene therapies using lentiviral vectors.
ϊγεγο 2023; 19(3), 205-210
Key words
hematopoietic stem cell, lentiviral vector, gene therapy, gene editing
Correspondence to
Naoya Uchida, Cellular and Molecular Therapeutics Branch (CMTB), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), 9000 Rockville Pike, Bethesda, Maryland 20892, USA
E-mailFuchidan@nhlbi.nih.gov
σtF2022N1115ϊ@σF2023N73ϊ |
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