In vitro selection of viral vectors with modified tropism:: The adeno-associated virus display
In vitro selection of viral vectors with modified tropism:: The adeno-associated virus display
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DOI：
10.1016/s1525-0016(03)00123-0
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发表时间：
2003-07-01
影响因子：
12.4
通讯作者：
Hallek, M
中科院分区：
文献类型：
--
作者：
Perabo, L;Büning, H;Hallek, M
提高基因载体的效率和特异性是基因治疗成功的关键。为了产生具有受控向性的病毒突变体，我们产生了具有随机修饰衣壳的腺相关病毒（AAV）克隆文库，并将其用于选择受体靶向突变体。在对野生型（wt）AAV感染具有抗性的不同细胞系进行几轮选择后，以高滴度收获感染性突变体。这些突变体以受体特异性方式转导靶细胞，效率增加高达100倍，并且不与wt AAV的主要受体相互作用。结果首次证明，基于真核病毒文库的组合方法允许产生具有所需向性的有效的受体特异性靶向载体。
Improving the efficiency and specificity of gene vectors is critical for the success of gene therapy. In an effort to generate viral mutants with controlled tropism we produced a library of adeno-associated virus (AAV) clones with randomly modified capsids and used it for the selection of receptor-targeting mutants. After several rounds of selection on different cell lines that were resistant to infection by wild-type (wt) AAV, infectious mutants were harvested at high titers. These mutants transduced target cells with an up to 100-fold increased efficiency, in a receptor-specific manner and without interacting with the primary receptor for wt AAV. The results demonstrate for the first time that a combinatorial approach based on a eukaryotic virus library allows one to generate efficient, receptor-specific targeting vectors with desired tropism.