Biodistribution of a low dose of intravenously administered AAV-2, 10, and 11 vectors to cynomolgus monkeys.

In gene therapy trials, adeno-associated virus (AAV) vectors are injected directly into target tissues such as muscle and liver. Direct injection can lead to the introduction of a low level of the vector into blood circulation. To determine the systemic effects of the vector released in the blood, we extensively examined the biodistribution of intravenously administered AAV serotype 2 (AAV2) vector in cynomolgus monkeys. Although the vector distribution pattern varied from monkey to monkey, the vector DNA was maintained in the various tissues beyond 7 months post-inoculation (pi). The vector DNA was detected in the lymphoid tissues, particularly in the spleen, more frequently and at a much higher level than in the other tissues tested (i.e., brain, lung, liver, heart, gallbladder, pancreas, colon, kidney, ovary, uterus, etc.). The expression of a transgene was detected in the lymph nodes at 3 months pi. The distribution of two pseudotyped vectors, AAV2/10 and AAV2/11, was similar to that of the AAV2 vector. The present results suggest that when introduced intravenously, the AAV vector DNA persists and may induce transgene expression in various monkey tissues. Thus, the possibility of inadvertent gene transfer to various non-target tissues should be considered in a gene therapy strategy with an AAV vector.