Evaluating clinically translatable conditioning for platelet gene therapy in murine hemophilia A with inhibitors.

ABSTRACT:

Background

Platelet gene therapy is effective in hemophilia A (HA) mice even with inhibitors. Fludarabine (Flu), along with busulfan (Bu) or melphalan (Mel), preconditioning has been shown to be highly effective for hematopoietic stem cell transplantation in the clinic.

Objectives

To evaluate the efficacy of Bu-Flu and Mel-Flu preconditioning in platelet gene therapy of HA with inhibitors.

Methods

Bu-Flu and Mel-Flu were used to condition HA mice preimmunized with recombinant human factor (F)VIII. An optimal 660 centigray total body irradiation was used as a control regimen in parallel. Platelet-FVIII expression was introduced by transplantation of 2bF8 lentivirus (LV)-transduced hematopoietic stem cells. Animals were analyzed by fluorescence-activated cell sorting, q

SUBMITTER: Chen Y 

PROVIDER: S-EPMC11513242 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature