Robust systemic transduction with AAV9 vectors in mice: Efficient global cardiac gene transfer superior to that of AAV8
Robust systemic transduction with AAV9 vectors in mice: Efficient global cardiac gene transfer superior to that of AAV8
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DOI：
10.1016/j.ymthe.2006.03.014
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发表时间：
2006-07-01
影响因子：
12.4
通讯作者：
Nakai, Hiroyuki
中科院分区：
文献类型：
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作者：
Inagaki, Katsuya;Fuess, Sally;Nakai, Hiroyuki
最近的研究表明，重组腺相关病毒血清8型(RAAV8)是一种强大的替代血清型载体，它克服了rAAV2的许多局限性，通过全身给药有效地、全球地转导了各种组织。AAV9是新近从人体组织中分离到的一种血清型，但目前我们对rAAV9在体内的生物学了解有限。在这里，我们通过一系列全面的并列实验，证明了rAAV8和9载体通过不同途径或不同剂量输送到小鼠身上，rAAV9载体具有rAAV8的稳健性，即(1)无论载体是血管内还是血管外给药，都具有非常高的肝脏转导效率，(2)通过外周静脉注射在心脏、骨骼肌和胰腺进行大量转导。重要的是，rAAV9转导的心肌细胞比rAAV8高5到10倍，导致尾静脉注射低至1.0×10(11)颗粒/只的小鼠后，超过80%的心肌细胞转导。因此，rAAV9和rAAV8在基因治疗应用中都是一个强大的载体，而rAAV9在通过全身载体输送心脏基因方面优于rAAV8。
It has been recently shown that recombinant adeno-associated virus serotype 8 (rAAV8) is a robust alternative serotype vector that overcomes many of the limitations of rAAV2 and transduces various tissues efficiently and globally through systemic vector administration. AAV9 is a serotype newly isolated from human tissues, but our knowledge of the biology of rAAV9 in vivo is currently limited. Here, we demonstrate by a series of comprehensive side-by-side experiments with rAAV8 and 9 vectors delivered via different routes or at various doses in mice that rAAV9 vectors share the robustness of rAAV8, i.e., (1) very high liver transduction efficiency irrespective of whether vectors are administered intravascularly or extravascularly and (2) substantial transduction in the heart, skeletal muscle, and pancreas by peripheral vein injection. Importantly, rAAV9 transduced myocardium 5- to 10-fold higher than rAAV8, resulting in over 80% cardiomyocyte transduction following tail vein injection of as low as 1.0 X 10(11) particles per mouse. Thus rAAV9, as well as rAAV8, is a robust vector for gene therapy applications and rAAV9 is superior to rAAV8 specifically for cardiac gene delivery by systemic vector administration.