Immunotherapy based on genetic modification of T cells has played an important role in the treatment of tumors and viral infections. Moreover, adenoviral vectors engineered with improved safety due to their inability to integrate into the host genome have been key in the clinical application of T cell therapy. However, the commonly used adenoviral vector Ad5 exhibits low efficiency of infection of human T cells and the details of the intracellular trafficking pathway of adenoviral vectors in human primary T cells remains unclear. Resolution of these issues will depend on successful modification of the adenoviral vector. To this end, here we describe the successful establishment of a simple and efficient method for editing adenoviral vectors in vitro using the CRISPR-Cas9 gene editing system to target the adenoviral fiber gene.

基于T细胞基因改造的免疫疗法在肿瘤和病毒感染的治疗中发挥了重要作用。此外，由于无法整合到宿主基因组中而具有更高安全性的腺病毒载体已成为 T 细胞治疗临床应用的关键。然而，常用的腺病毒载体 Ad5 对人 T 细胞的感染效率低，腺病毒载体在人原代 T 细胞中的细胞内运输途径的细节仍不清楚。这些问题的解决将取决于腺病毒载体的成功修饰。为此，我们在此描述了使用 CRISPR-Cas9 基因编辑系统靶向腺病毒纤维，成功建立了一种简单有效的体外编辑腺病毒载体的方法。基因。