Helen Wills Neuroscience Institute, The University of California Berkeley, 112 Barker Hall, 94720, Berkeley, CA, USA,
Adv Exp Med Biol. 2014;801:687-93. doi: 10.1007/978-1-4614-3209-8_86.
Adeno-associated virus (AAV) is a small, non-pathogenic dependovirus that has shown great potential for safe and long-term expression of a genetic payload in the retina. AAV has been used to treat a growing number of animal models of inherited retinal degeneration, though drawbacks-including a limited carrying capacity, slow onset of expression, and a limited ability to transduce some retinal cell types from the vitreous-restrict the utility of AAV for treating some forms of inherited eye disease. Next generation AAV vectors are being created to address these needs, through rational design efforts such as the creation of self-complementary AAV vectors for faster onset of expression and specific mutations of surface-exposed residues to increase transduction of viral particles. Furthermore, directed evolution has been used to create, through an iterative process of selection, novel variants of AAV with newly acquired, advantageous characteristics. These novel AAV variants have been shown to improve the therapeutic potential of AAV vectors, and further improvements may be achieved through rational design, directed evolution, or a combination of these approaches, leading to broader applicability of AAV and improved treatments for inherited retinal degeneration.
腺相关病毒（AAV）是一种小型、非致病性的依赖病毒，在视网膜中安全且长期表达遗传有效载荷方面具有巨大潜力。AAV 已被用于治疗越来越多的遗传性视网膜变性动物模型，但存在一些局限性，包括载量有限、表达起始缓慢，以及从玻璃体内转导某些视网膜细胞类型的能力有限，这些都限制了 AAV 治疗某些遗传性眼病的应用。通过理性设计等努力，正在开发下一代 AAV 载体来满足这些需求，例如创建自我互补的 AAV 载体以加快表达起始速度，以及对表面暴露残基进行特定突变以增加病毒颗粒的转导。此外，通过反复的选择过程，定向进化已被用于创造具有新获得的有利特征的新型 AAV 变体。这些新型 AAV 变体已被证明可提高 AAV 载体的治疗潜力，并且通过理性设计、定向进化或这些方法的组合，可能会进一步提高治疗效果，从而扩大 AAV 的适用性并改善遗传性视网膜变性的治疗效果。
