Table 1.

Advantages and disadvantages of new strategies to correct hemophilia A

Gene vector	Target	Gene promoter	FVIII	Reference	Advantages	Disadvantages
AAV	Endothelium liver	Liver specific	BDD FVIII modified	61	+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
LV	HSC CD34+ PBSCs	Nonspecific CMV	BDD FVIII modified	63	+Use with AAV inhibitors	−Submyeloablative conditioning required
						−Mutagenesis risk
					+Theoretically 1 treatment	−Use only without FVIII inhibitor
LV	HSC CD34+ PBSCs	Meg-GPIBA	BDD FVIII modified	67	+Use with AAV and FVIII inhibitors	−Submyeloablative conditioning required
					+Theoretically 1 treatment	−Mutagenesis risk
						−GPIBA gene promoter associated with low plt production
LV	HSC BM	Meg-GPIBA	BDD FVIII	72	+No pre-tx conditioning	−Target cell not purified for transduction
						−Mutagenesis risk
					+Use with AAV and FVIII inhibitors	−GPIBA gene promoter associated with low plt production
					+Theoretically 1 treatment	−Feasibility in humans?
LV	HSC CD34+ PBSCs	Meg-ITGA2B	BDD FVIII	31	+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.