Design and self-assembly of simple coat proteins for artificial viruses
Design and self-assembly of simple coat proteins for artificial viruses
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DOI：
10.1038/nnano.2014.169
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发表时间：
2014-09-01
影响因子：
38.3
通讯作者：
de Vries, Renko
中科院分区：
文献类型：
--
作者：
Hernandez-Garcia, Armando;Kraft, Daniela J.;de Vries, Renko
病毒是最简单的生物系统之一，是将遗传物质传递到易感宿主细胞的高效载体(1)。人工病毒可以用作模型系统，以提供对自然病毒的深入了解，并且可以被视为开发人工生命的试验场。此外，它们还用于生物医学和生物技术应用，例如靶向递送核酸用于基因治疗（1,2）和作为材料科学的支架（3-5）。在自然环境下，病毒的生存需要很大一部分复制的基因组被外壳蛋白完全保护。基因组的完全保护是由外壳蛋白和核酸之间高度合作的超分子过程确保的，这一过程仅基于可逆、弱和变构相互作用（6-9）。然而，将这种类型的超分子协同性纳入人工病毒仍然具有挑战性（10-15）。在这里，我们报告了一种基于简单多肽结构域的自组装最小病毒外壳蛋白的合理设计。我们的外壳蛋白具有精确控制其自组装与单个DNA分子的协同性，最终形成棒状病毒样颗粒。我们证实了我们的设计原则的有效性，表明我们的病毒样颗粒的自组装动力学遵循先前为烟草花叶病毒开发的模型(9)。我们表明，我们的病毒样颗粒保护DNA免受酶降解，并以相当高的效率转染细胞，使它们成为有希望的递送载体。
Viruses are among the simplest biological systems and are highly effective vehicles for the delivery of genetic material into susceptible host cells(1). Artificial viruses can be used as model systems for providing insights into natural viruses and can be considered a testing ground for developing artificial life. Moreover, they are used in biomedical and biotechnological applications, such as targeted delivery of nucleic acids for gene therapy(1,2) and as scaffolds in material science(3-5). In a natural setting, survival of viruses requires that a significant fraction of the replicated genomes be completely protected by coat proteins. Complete protection of the genome is ensured by a highly cooperative supramolecular process between the coat proteins and the nucleic acids, which is based on reversible, weak and allosteric interactions only(6-9). However, incorporating this type of supramolecular cooperativity into artificial viruses remains challenging(10-15). Here, we report a rational design for a self-assembling minimal viral coat protein based on simple polypeptide domains. Our coat protein features precise control over the cooperativity of its self-assembly with single DNA molecules to finally form rod-shaped virus-like particles. We confirm the validity of our design principles by showing that the kinetics of self-assembly of our virus-like particles follows a previous model developed for tobacco mosaic virus(9). We show that our virus-like particles protect DNA against enzymatic degradation and transfect cells with considerable efficiency, making them promising delivery vehicles.