重组腺相关病毒载体基因表达效率与辐射的关系

Relationship between radiations and expression efficiency of recombinant adeno-associated virus vector

摘要:

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。

Abstract:

Recombinant adeno-associated virus (rAAV) vector, one of the most promising vectors, has been widely used in clinical trials for gene therapy. However, the contradiction between the effectiveness of gene delivery and the immunogenicity of viral capsid protein restricts the development of gene drugs designed based on this vector. Thus, improving the transduction efficiency is one of the most important research fields for rAAV vector. Recent results showed that radiations, such as UV light and γ-ray, can significantly improve the gene expression efficiency of rAAV vector in various types of cells and tissues. These effects vary across the radiation types and doses, the cell types and statuses, the time and infection index of vectors. It is proposed that DNA damage responses (especially for double strand break repair) induced by radiations might contribute to improve transgene expression of rAAV vector. A better understanding of the relationship between radiations and rAAV gene expression will facilitate the combination use of these two strategies in disease therapy. This review discussed the mechanism of UV and γ-ray radiation to improve the expression efficiency of rAAV, the influencing factors as well as the application and progress of it in the field of gene therapy.