Model of the relationship between capsid dose and outcome of gene transfer following systemic vector delivery. Low capsid doses are more likely to be neutralized by anti-AAV antibodies, even low-titer NAb. This results in lack of efficacy. Higher capsid doses overcome this limitation, leading to therapeutic efficacy. Capsid-specific T-cell activation is detected as the total capsid dose administered increases. This does not affect efficacy until a critical threshold is reached, above which immune-mediated clearance of transduced target cells results in loss of efficacy.