CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
人细胞中 130 个 DNA 转座子的异源调查揭示其功能分化并拓展基因组工程工具箱
英文原题：Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox.
查看英文原题
Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
以往 DNA 转座元件（TE）的实验研究规模有限，因此人们对影响转座活性、进化动态及其作为基因组工程工具应用潜力的因素了解不足。我们从 102 个后生动物基因组中预测出 130 种活性 DNA TE，并评估其在人细胞中的活性。研究鉴定出 40 种具有活性（具备整合能力）的 TE，超过既往发现的 TE 总数（20 种）。利用这一统一的比较数据，我们发现 Tc1/mariner 超家族活性升高，这可能解释其广泛的水平转移现象。对 TE 的进一步功能表征还揭示了插入偏好等特征方面的额外差异。值得注意的是，在治疗血液系统恶性肿瘤和实体瘤的 CAR-T 疗法中，已鉴定出的最活跃 DNA TE——Mariner2_AG（MAG）——表现远优于两种广泛使用的载体：慢病毒载体和基于 TE 的 SB100X 载体。总之，本研究揭示 DNA TE 转座特征及进化动态的多样性，并丰富了 TE 工具库。
展开英文摘要原文
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.
论文信息
- 作者
- Zhang T、Tan S、Tang N、Li Y、Zhang C、Sun J、Guo Y、Gao H
- 第一作者单位
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.China
- 通讯作者单位
- University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: zhangyong@ioz.ac.cn.China
- 期刊
- Cell2024 Jul 11
- 原文标识
- PubMed 38843831 · DOI 10.1016/j.cell.2024.05.007