Discovery and protein language model-guided design of hyperactive transposases.
basic_science · Level V
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- Record sourced from PubMed, PMID 41039042.
- Also identified by DOI 10.1038/s41587-025-02816-4.
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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.