Gene therapy with adeno-associated virus (AAV)-based vectors shows great promise for the gene therapeutic treatment of a broad array of diseases. In fact, the treatment of genetic diseases with AAV vectors is currently the only in vivo gene therapy approach that is approved by the US Food and Drug Administration (FDA). Unfortunately, pre-existing antibodies against AAV severely limit the patient population that can potentially benefit from AAV gene therapy, especially if the vector is delivered by intravenous injection. Here, we demonstrate that we can selectively deplete anti-AAV antibodies by hemapheresis combined with AAV9 particles coupled to Sepharose beads. In rats that underwent hemapheresis and immunoadsorption, luciferase expression was dramatically increased in the hearts and fully restored in the livers of these rats. Importantly, our method can be readily adapted for the use in clinical AAV gene therapy.

中文翻译：

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通过免疫吸附选择性清除抗AAV抗体后，成功用AAV载体转导。

使用基于腺相关病毒（AAV）的载体进行的基因治疗对多种疾病的基因治疗具有广阔的前景。实际上，使用AAV载体治疗遗传性疾病目前是美国食品和药物管理局（FDA）批准的唯一体内基因治疗方法。不幸的是，针对AAV的预先存在的抗体严重限制了可能从AAV基因治疗中受益的患者人群，特别是如果通过静脉注射递送载体的情况。在这里，我们证明了我们可以通过与结合琼脂糖珠的AAV9颗粒结合的血液置换术选择性地去除抗AAV抗体。在经历了血液置换和免疫吸附的大鼠中，萤光素酶的表达在心脏中急剧增加，并在这些大鼠的肝脏中完全恢复。重要的，