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<p>The diversity and biochemical potential of the <i>PiggyBac</i> transposase gene insertion system remains largely unexplored. Using a eukaryotic transposon mining pipeline, we expand the explored diversity by two orders of magnitude and experimentally validate a subset of highly divergent <i>PiggyBac</i> sequences. Fine-tuning a protein language model to further expand <i>PiggyBac</i> sequence space discovers transposases with improved activity and that are compatible with T cell engineering and Cas9-directed transposase-assisted integration.</p>

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Discovery and protein language model-guided design of hyperactive transposases

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月2日

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  • Dimitrije Ivančić,
  • Alejandro Agudelo,
  • Jonathan Lindstrom-Vautrin,
  • Jessica Jaraba-Wallace,
  • Maria Gallo,
  • Ravi Das,
  • Alejandro Ragel,
  • Jorge Herrero-Vicente,
  • Irene Higueras,
  • Federico Billeci,
  • Marta Sanvicente-García,
  • Paolo Petazzi,
  • Noelia Ferruz,
  • Avencia Sánchez-Mejías,
  • Marc Güell

摘要

The diversity and biochemical potential of the PiggyBac transposase gene insertion system remains largely unexplored. Using a eukaryotic transposon mining pipeline, we expand the explored diversity by two orders of magnitude and experimentally validate a subset of highly divergent PiggyBac sequences. Fine-tuning a protein language model to further expand PiggyBac sequence space discovers transposases with improved activity and that are compatible with T cell engineering and Cas9-directed transposase-assisted integration.