Mori Seiichiro, Takeuchi Takamasa, Enomoto Yutaka, Kondo Kazunari, Sato Kaori, Ono Fumiko, Iwata Naoko, Sata Tetsutaro, Kanda Tadahito
Center for Pathogen Genomics, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Jpn J Infect Dis. 2006 Oct;59(5):285-93.
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.
在基因治疗试验中，腺相关病毒（AAV）载体被直接注射到肌肉和肝脏等靶组织中。直接注射可能会导致少量载体进入血液循环。为了确定血液中释放的载体的全身效应，我们广泛研究了静脉注射2型腺相关病毒（AAV2）载体在食蟹猴体内的生物分布。尽管不同猴子之间的载体分布模式有所不同，但接种后7个月以上，载体DNA仍保留在各种组织中。在淋巴组织中，尤其是在脾脏中，检测到载体DNA的频率更高，水平也比其他测试组织（即脑、肺、肝、心、胆囊、胰腺、结肠、肾、卵巢、子宫等）高得多。接种后3个月，在淋巴结中检测到转基因表达。两种假型载体AAV2/10和AAV2/11的分布与AAV2载体相似。目前的结果表明，静脉注射时，AAV载体DNA会持续存在，并可能在各种猴子组织中诱导转基因表达。因此，在使用AAV载体的基因治疗策略中，应考虑无意中将基因转移到各种非靶组织的可能性。
