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重组腺相关病毒(rAAV)载体被认为是最有希望的临床应用基因治疗载体之一。rAAV载体基因传递的有效性与病毒衣壳蛋白的免疫原性之间的矛盾是制约该类基因药物开发的关键难题,提高其表达效率是rAAV载体研发的主攻方向之一。研究发现,紫外线、γ射线等辐射可以提高rAAV载体的基因表达效率,其作用效果与辐射种类和剂量、细胞种类和状态、载体感染指数和感染时间等因素有关。其机制可能与DNA损伤反应,特别是DNA双链断裂修复有关。对辐射与rAAV载体的表达效率之间关系的深入了解,为两者的联合应用打开方便之门。本文将对UV、γ射线等辐射提高rAAV载体表达效率的机制、影响因素及其在基因治疗领域的应用进展进行综述。
Recombinant adeno-associated virus (rAAV) vectors are considered as one of the most promising vector for clinical application of gene therapy. The contradiction between the effectiveness of gene delivery of rAAV vector and the immunogenicity of virus capsid protein is the key problem restricting the development of this kind of gene drug. To improve the expression efficiency of rAAV vector is one of the main research directions of rAAV vector. The study found that ultraviolet radiation, γ-ray and other radiation can improve the gene expression efficiency of rAAV vector, and its effects and radiation types and doses, cell types and status, vector infection index and infection time and other factors. The mechanism may be DNA damage response, especially DNA double-strand break repair. A deep understanding of the relationship between radiation and the efficiency of expression of rAAV vectors opens the door to a combination of the two. This review summarizes the mechanisms, influencing factors and their application in the field of gene therapy to enhance the expression efficiency of rAAV vector by UV, γ-ray and other radiation.