Cas9-Cleavage Sequences in Size-Reduced Plasmids Enhance Nonviral Genome Targeting of CARs in Primary Human T Cells
Cas9-Cleavage Sequences in Size-Reduced Plasmids Enhance Nonviral Genome Targeting of CARs in Primary Human T Cells
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DOI：
10.1002/smtd.202100071
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发表时间：
2021-05-19
期刊：
影响因子：
12.4
通讯作者：
Sun, Jie
中科院分区：
文献类型：
--
作者：
Jing, Ruirui;Jiao, Peng;Sun, Jie
T细胞基因组编辑在推进一系列免疫疗法方面有很大的希望，但由于依赖于难以生产和昂贵的病毒载体而受到阻碍。在这里，设计了经修饰以介导高效同源重组的小双链质粒DNA。所得嵌合抗原受体（CAR）-T细胞显示出与使用腺相关病毒载体产生的CAR-T细胞相似的表型、转录谱和体内效力。这种方法应该简化和加速精密工程的使用，以生产用于研究和临床目的的编辑T细胞。
T cell genome editing holds great promise to advance a range of immunotherapies but is encumbered by the dependence on difficult-to-produce and expensive viral vectors. Here, small double-stranded plasmid DNA modified to mediate high-efficiency homologous recombination is designed. The resulting chimeric antigen receptor (CAR)-T cells display a similar phenotype, transcriptional profile, and in vivo potency to CAR-T cells generated using adeno-associated viral vector. This method should simplify and accelerate the use of precision engineering to produce edited T cells for research and clinical purposes.