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CAR-T疗法
CELL · 2024 · IF 45.5

Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox

Tongtong Zhang,Shengjun Tan,Na Tang,Yuanqing Li,Chenze Zhang,Jing Sun,Yanyan Guo,Hui Gao,Yujia Cai,Wen Sun,Chenxin Wang,Liangzheng Fu,Huijing Ma,Yachao Wu,Xiaoxuan Hu,Xuechun Zhang,Peter Gee,Weihua Yan,Yahui Zhao,Qiang Chen,Baocheng Guo,Haoyi Wang,Yong E. Zhang

Experimental studies on DNA transposable elements (TEs) have been limited in scale, leading to a lack of understanding of the factors influencing transposition activity, evolutionary dynamics, and application potential as genome engineering tools. We predicted 130 active DNA TEs from 102 metazoan genomes and evaluated their activity in human cells. We identified 40 active (integration-competent) TEs, surpassing the cumulative number (20) of TEs found previously. With this unified comparative data, we found that the Tc1/ mariner superfamily exhibits elevated activity, potentially explaining their pervasive horizontal transfers. Further functional characterization of TEs revealed additional divergence in features such as insertion bias. Remarkably, in CAR-T therapy for hematological and solid tumors, Mariner2_AG (MAG), the most active DNA TE identified, largely outperformed two widely used vectors, the lentiviral vector and the TE-based vector SB100X. Overall, this study highlights the varied transposition features and evolutionary dynamics of DNA TEs and increases the TE toolbox diversity.

CAS / MDL: 30525-89-4
研究领域: 分子生物学 · 遗传学 · 基因组学 · 医学
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