HMBS and acute intermittent porphyria: In our animals, intravenous delivery of rAAV5 activates significant humoral responses to AAV capsids but not to the cytosolic transgene product, which in the case of PBGD is an endogenously expressed protein that is highly conserved (99.2 % identity) between humans and macaca. Most probably, PBGD transgene protein will not elicit immune responses in a clinical trial for acute intermittent porphyria because the normal allele of PBGD produced in all cells from these patients should have induced immunological tolerance to the identical pbgd transgene-encoded protein.