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

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

Cell

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:

Published: July 2024

AI Article Synopsis

  • - This study focused on understanding DNA transposable elements (TEs) by predicting 130 active TEs from 102 metazoan genomes and testing their activity in human cells, identifying 40 active ones, which is double the number previously known.
  • - The research found that the Tc1/mariner superfamily has higher transposition activity, suggesting why these elements are frequently transferred between species.
  • - In a significant application, the most active TE, Mariner2_AG (MAG), was shown to be more effective than traditional vectors in CAR-T cancer therapy, underscoring the diverse potential of TEs in genome engineering.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.cell.2024.05.007DOI Listing

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