β-thalassemias constitute hereditary blood disorders characterized by reduced or absence of
β-globin synthesis resulting in mild to severe anemia, depending on the genotype. More than 200 mutations in
the β-globin gene are responsible for their specific features leading to a very heterogeneous phenotype.
Current therapies for β-thalassemia include blood transfusions, usually along with iron chelation and in
selected cases with bone marrow transplantation (BMT) of HLA-matched hematopoietic stem cells (HSCs).
However, these approaches are limited by factors, such as iron overload and donor availability, respectively.
Since 2000, when globin lentiviral vectors (LVs) were first successfully tested for transfer efficiency of the
therapeutic transgene, which led to disease amelioration in murine models, attention was drawn towards the
improvement of such vectors for β-thalassemia gene therapy. Constantly improving vector design and efficient
HSC manipulation led recently to the first successful clinical trial in France, which further proved that this
genetic approach can be curative. Furthermore, improved new efficient vectors and methods to safely monitor
integration sites and therapeutic transgene position effects, promise a new era for β-thalassemia gene therapy,
with more and safer clinical trials yet to come.
Keywords: β-thalassemia, clinical trial, CD34+ cells, gene therapy, γ-globin, hematopoietic stem cells (HSCs),
lentiviral vectors (LVs).
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