Site-Specific Post-translational Surface Modification of Adeno-Associated Virus Vectors Using Leucine Zippers.,ACS Synthetic Biology

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Site-Specific Post-translational Surface Modification of Adeno-Associated Virus Vectors Using Leucine Zippers.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-02-18 , DOI: 10.1021/acssynbio.9b00341
Nicole N Thadani ₁ , Joanna Yang ₁ , Buhle Moyo ₁ , Ciaran M Lee ₁ , Maria Y Chen ₁ , Gang Bao ₁ , Junghae Suh _{1,

2,

3,

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Affiliation

Adeno-associated virus (AAV) is widely favored as a gene therapy vector, tested in over 200 clinical trials internationally. To improve targeted delivery a variety of genetic capsid modifications, such as insertion of targeting proteins/peptides into the capsid shell, have been explored with some success but larger insertions often have unpredictable deleterious impacts on capsid formation and gene delivery. Here, we demonstrate a modular platform for the integration of exogenous peptides and proteins onto the AAV capsid post-translationally while preserving vector functionality. We decorated the AAV capsid with leucine-zipper coiled-coil binding motifs that exhibit specific noncovalent heterodimerization. AAV capsids successfully display hexahistidine tagged-peptides using this approach, as demonstrated through nickel column affinity. This protein display platform may facilitate the incorporation of biological moieties on the AAV surface, expanding possibilities for vector enhancement and engineering.

中文翻译：

使用亮氨酸拉链对腺相关病毒载体进行位点特异性翻译后表面修饰。

腺相关病毒 (AAV) 作为基因治疗载体受到广泛青睐，已在国际上进行了 200 多项临床试验。为了改善靶向递送，各种遗传衣壳修饰，例如将靶向蛋白/肽插入衣壳壳中，已经取得了一些成功，但较大的插入通常会对衣壳形成和基因递送产生不可预测的有害影响。在这里，我们展示了一个模块化平台，用于将外源肽和蛋白质翻译后整合到 AAV 衣壳上，同时保留载体功能。我们用亮氨酸拉链卷曲螺旋结合基序装饰 AAV 衣壳，这些基序表现出特定的非共价异二聚化。通过镍柱亲和力证明，AAV 衣壳使用这种方法成功展示了六组氨酸标记的肽。该蛋白质展示平台可以促进生物部分在 AAV 表面的掺入，扩大载体增强和工程的可能性。

更新日期：2020-02-18

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