Viruses can be engineered to efficiently deliver exogenous genes, but their natural gene delivery properties often fail to meet human therapeutic needs. Therefore, engineering viral vectors with new properties, including enhanced targeting abilities and resistance to immune responses, is a growing area of research. This review discusses protein engineering approaches to generate viral vectors with novel gene delivery capabilities. Rational design of viral vectors has yielded successful advances in vitro, and to an extent in vivo. However, there is often insufficient knowledge of viral structure-function relationships to reengineer existing functions or create new capabilities, such as virus-cell interactions, whose molecular basis is distributed throughout the primary sequence of the viral proteins. Therefore, high-throughput library and directed evolution methods offer alternative approaches to engineer viral vectors with desired properties. Parallel and integrated efforts in rational and library-based design promise to aid the translation of engineered viral vectors toward the clinic.

中文翻译：

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病毒基因传递载体的分子工程。

病毒可以被设计为有效地传递外源基因，但它们的天然基因传递特性通常不能满足人类的治疗需求。因此，设计具有新特性的病毒载体，包括增强的靶向能力和对免疫反应的抵抗力，是一个不断增长的研究领域。这篇综述讨论了蛋白质工程方法来生成具有新型基因传递能力的病毒载体。病毒载体的合理设计在体外和一定程度上在体内取得了成功。然而，通常对病毒结构-功能关系的了解不足以重新设计现有功能或创造新功能，例如病毒-细胞相互作用，其分子基础分布在病毒蛋白质的整个一级序列中。所以，高通量文库和定向进化方法为设计具有所需特性的病毒载体提供了替代方法。合理和基于库的设计中的并行和综合努力有望帮助将工程病毒载体转化为临床。