Rutledge E A, Halbert C L, Russell D W
Division of Hematology and Markey Molecular Medicine Center, University of Washington, Seattle 98195, USA.
J Virol. 1998 Jan;72(1):309-19. doi: 10.1128/JVI.72.1.309-319.1998.
Adeno-associated viruses (AAVs) are single-stranded dependent parvoviruses being developed as transducing vectors. Although at least five serotypes exist (AAV types 1 to 5 [AAV1 to -5]), only AAV2, AAV3, and AAV4 have been sequenced, and the vectors in use were almost all derived from AAV2. Here we report the cloning and sequencing of a second AAV3 genome and a new AAV serotype designated AAV6 that is related to AAV1. AAV2, AAV3, and AAV6 were 82% identical at the nucleotide sequence level, and AAV4 was 75 to 78% identical to these AAVs. Significant sequence variation was noted in portions of the capsid proteins that presumably are responsible for serotype-specific functions. Vectors produced from AAV3 and AAV6 differed from AAV2 vectors in host range and serologic reactivity. The AAV3 and AAV6 vector serotypes were able to transduce cells in the presence of serum from animals previously exposed to AAV2 vectors. Our results suggest that vectors based on alternative AAV serotypes will have advantages over existing AAV2 vectors, including the transduction of different cell types, and resistance to neutralizing antibodies against AAV2. This could be especially important for gene therapy, as significant immunity against AAV2 exists in human populations and many protocols will likely require multiple vector doses.
腺相关病毒（AAV）是作为转导载体而被开发的单链依赖细小病毒。尽管至少存在五种血清型（AAV 1型至5型[AAV1至-5]），但仅对AAV2、AAV3和AAV4进行了测序，并且所使用的载体几乎都源自AAV2。在此我们报告了第二个AAV3基因组以及一种与AAV1相关的新AAV血清型（命名为AAV6）的克隆和测序。AAV2、AAV3和AAV6在核苷酸序列水平上有82%的同一性，而AAV4与这些AAV的同一性为75%至78%。在衣壳蛋白的部分区域注意到显著的序列变异，推测这些区域负责血清型特异性功能。由AAV3和AAV6产生的载体在宿主范围和血清学反应性方面与AAV2载体不同。AAV3和AAV6载体血清型能够在存在先前接触过AAV2载体的动物血清的情况下转导细胞。我们的结果表明，基于其他AAV血清型的载体将比现有的AAV2载体具有优势，包括转导不同细胞类型以及对针对AAV2的中和抗体具有抗性。这对于基因治疗可能尤为重要，因为人类群体中存在对AAV2的显著免疫力，并且许多方案可能需要多次给予载体剂量。
