Adeno-associated virus (AAV) vector-directed gene therapy is one of the most exciting modalities of biotechnology as more applications enter clinical stage. Although AAV vectors generally feature low toxicity, high stability, and long-lasting transgene expression, potential challenging issues of AAV include high vector dose, limited tissue tropism, and the host immune response and inflammation, which are all related to the capsid protein. To overcome these challenges, various strategies have been developed to engineer AAV capsids. Apart from widely employed genetic engineering of capsid protein, powerful and versatile chemical modification strategies are underexploited. This minireview summarizes recent advances and our perspectives for future direction in AAV capsid chemical modification to enhance its therapeutic use for gene therapy.

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用于重定向和提高腺相关病毒载体功效的衣壳化学修饰

随着越来越多的应用进入临床阶段，腺相关病毒 (AAV) 载体定向基因治疗是生物技术中最令人兴奋的方式之一。虽然 AAV 载体通常具有低毒性、高稳定性和长效转基因表达的特点，但 AAV 潜在的挑战问题包括高载体剂量、有限的组织嗜性以及宿主免疫反应和炎症，这些都与衣壳蛋白有关。为了克服这些挑战，已经开发了各种策略来设计 AAV 衣壳。除了广泛采用的衣壳蛋白基因工程外，强大而通用的化学修饰策略尚未得到充分利用。这篇迷你评论总结了 AAV 衣壳化学修饰的最新进展和我们对未来方向的展望，以增强其在基因治疗中的治疗用途。