Laboratory of Genome Editing, Research Centre for Medical Genetics, Moskvorechye, 1, 115522 Moscow, Russia.
Int J Mol Sci. 2024 Nov 20;25(22):12461. doi: 10.3390/ijms252212461.
Adenoviral vectors (AdVs) are effective vectors for gene therapy due to their broad tropism, large capacity, and high transduction efficiency, making them widely used as oncolytic vectors and for creating vector-based vaccines. This review also considers the application of adenoviral vectors in oncolytic virotherapy and gene therapy for inherited diseases, analyzing strategies to enhance their efficacy and specificity. However, despite significant progress in this field, the use of adenoviral vectors is limited by their high immunogenicity, low specificity to certain cell types, and limited duration of transgene expression. Various strategies and technologies aimed at improving the characteristics of adenoviral vectors are being developed to overcome these limitations. Significant attention is being paid to the creation of tissue-specific promoters, which allow for the controlled expression of transgenes, as well as capsid modifications that enhance tropism to target cells, which also play a key role in reducing immunogenicity and increasing the efficiency of gene delivery. This review focuses on modern approaches to adenoviral vector modifications made to enhance their effectiveness in gene therapy, analyzing the current achievements, challenges, and prospects for applying these technologies in clinical practice, as well as identifying future research directions necessary for successful clinical implementation.
腺病毒载体（AdVs）由于其广泛的嗜性、大容量和高转导效率，是基因治疗的有效载体，因此被广泛用作溶瘤载体和用于创建基于载体的疫苗。本综述还考虑了腺病毒载体在溶瘤病毒治疗和遗传性疾病的基因治疗中的应用，分析了增强其疗效和特异性的策略。然而，尽管在该领域取得了重大进展，但腺病毒载体的使用受到其高免疫原性、对某些细胞类型的低特异性和转基因表达持续时间有限的限制。正在开发各种旨在改善腺病毒载体特性的策略和技术，以克服这些限制。人们高度关注创建组织特异性启动子，这些启动子可以控制转基因的表达，以及增强对靶细胞的嗜性的衣壳修饰，这也在降低免疫原性和提高基因传递效率方面发挥着关键作用。本综述重点介绍了为增强腺病毒载体在基因治疗中的有效性而进行的现代修饰方法，分析了这些技术在临床实践中的当前成就、挑战和前景，并确定了成功临床实施所需的未来研究方向。
