Discovery and protein language model-guided design of hyperactive transposases.

IF 41.7 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2025-10-02 DOI:10.1038/s41587-025-02816-4

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

引用次数: 0

Abstract

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.

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多活性转座酶的发现和蛋白质语言模型引导的设计。

PiggyBac转座酶基因插入系统的多样性和生化潜力在很大程度上仍未被探索。利用真核转座子挖掘管道，我们将探索的多样性扩大了两个数量级，并通过实验验证了高度发散的PiggyBac序列子集。微调蛋白质语言模型以进一步扩大PiggyBac序列空间，发现具有改进活性的转座酶，并且与T细胞工程和cas9导向转座酶辅助整合兼容。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

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