对DNA转座因子(TEs)的实验研究规模有限,导致对影响换位活动的因素缺乏了解,进化动力学,以及作为基因组工程工具的应用潜力。我们从102个后生动物基因组中预测了130个活性DNATEs,并评估了它们在人类细胞中的活性。我们确定了40个活跃的(有整合能力的)TE,超过了以前发现的TEs的累计数量(20)。有了这些统一的比较数据,我们发现Tc1/mariner超家族表现出增强的活动,可能解释了它们普遍的水平转移。TE的进一步功能表征揭示了诸如插入偏差之类的特征的额外分歧。值得注意的是,在血液和实体瘤的CAR-T治疗中,Mariner2_AG(MAG),确定的最活跃的DNATE,在很大程度上优于两个广泛使用的载体,慢病毒载体和基于TE的载体SB100X。总的来说,这项研究突出了DNATEs的各种转座特征和进化动力学,并增加了TE工具箱的多样性.
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.