Table 1

Advantages and disadvantages of new strategies to correct hemophilia A

Gene vectorTargetGene promoterFVIIIReferenceAdvantagesDisadvantages
AAVEndothelium liverLiver specificBDD FVIII modified61+No pre-tx conditioning−Vector size limitation
+Shown safe in humans−Use only in patients without AAV inhibitor and without FVIII inhibitor
+No reports of mutagenesis−Cell death ends treatment
LVHSC CD34+ PBSCsNonspecific CMVBDD FVIII modified63+Use with AAV inhibitors−Submyeloablative conditioning required
−Mutagenesis risk
+Theoretically 1 treatment−Use only without FVIII inhibitor
LVHSC CD34+ PBSCsMeg-GPIBABDD FVIII modified67+Use with AAV and FVIII inhibitors−Submyeloablative conditioning required
+Theoretically 1 treatment−Mutagenesis risk
GPIBA gene promoter associated with low plt production
LVHSC BMMeg-GPIBABDD FVIII72+No pre-tx conditioning−Target cell not purified for transduction
−Mutagenesis risk
+Use with AAV and FVIII inhibitorsGPIBA gene promoter associated with low plt production
+Theoretically 1 treatment−Feasibility in humans?
LVHSC CD34+ PBSCsMeg-ITGA2BBDD FVIII31+Use with AAV and FVIII inhibitors−Submyeloablative conditioning required
+Normal plt production−Mutagenesis risk
  • BM, bone marrow; CMV, promoter of the cytomegalovirus; LV, lentiviral vector; Meg, megakaryocyte-specific; plt, platelet; tx, transplant.