Novel lentiviral vectors for gene therapy of sickle cell disease combining gene addition and gene silencing strategies.

ABSTRACT: Sickle cell disease (SCD) is due to a mutation in the β-globin gene causing production of the toxic sickle hemoglobin (HbS; α₂β^S ₂). Transplantation of autologous hematopoietic stem and progenitor cells (HSPCs) transduced with lentiviral vectors (LVs) expressing an anti-sickling β-globin (βAS) is a promising treatment; however, it is only partially effective, and patients still present elevated HbS levels. Here, we developed a bifunctional LV expressing βAS3-globin and an artificial microRNA (amiRNA) specifically downregulating β^S-globin expression with the aim of reducing HbS levels and favoring βAS3 incorporation into Hb tetramers. Efficient transduction of SCD HSPCs by the bifunctional LV led to a substantial decrease of β^S-globin t

SUBMITTER: Brusson M 

PROVIDER: S-EPMC10113710 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature