Enhancing therapeutic efficacy of in vivo platelet-targeted gene therapy in hemophilia A mice.

ABSTRACT: Our previous studies demonstrated that intraosseous (IO) infusion of lentiviral vectors (LVs) carrying a modified B domain-deleted factor VIII (FVIII) transgene driven by a megakaryocyte-specific promoter (GP1Bα promoter; G-F8/N6-LV) successfully transduced hematopoietic stem cells (HSCs) to produce FVIII stored in the platelet α-granules. Platelet FVIII corrected the bleeding phenotype with limited efficacy in hemophilia A (HemA) mice with and without preexisting anti-FVIII inhibitors. The present study sought to further enhance the therapeutic efficacy of this treatment protocol by increasing both the efficiency of LV transduction and the functional activity of platelet FVIII. A combined drug regimen of dexamethasone and anti-CD8α monoclonal antibody enhanced the percentage of transduced

SUBMITTER: Wang X 

PROVIDER: S-EPMC7686911 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature