Non-genotoxic conditioning facilitates hematopoietic stem cell gene therapy for hemophilia A using bioengineered factor VIII
Athena Russell, Chengyu Prince, Taran S. Lundgren, Kristopher A. Knight, Gabriela Denning, Jordan S. Alexander, Jaquelyn T. Zoine, H. Trent Spencer, Shanmuganathan Chandrakasan, Christopher B. Doering
Abstract
using recombinant lentiviral vector (LV) encoding a bioengineered high-expression factor VIII variant, termed ET3. Factor VIII procoagulant activity levels were durably elevated into the normal range and phenotypic correction achieved. Furthermore, no immunological rejection or development of anti-ET3 immunity was observed. These preclinical data support clinical translation of non-genotoxic antibody-based conditioning in HSPC LV gene therapy for HA.
Topics & Concepts
Genetic enhancementHaematopoiesisConditioningHematopoietic stem cellStem cellCancer researchBiologyGeneMedicineCell biologyGeneticsStatisticsMathematicsCAR-T cell therapy researchHemophilia Treatment and ResearchVirus-based gene therapy research