Publications
Nature biotechnologyOct 2025 DOI:
10.1038/s41587-025-02816-4

Discovery and protein language model-guided design of hyperactive transposases

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

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