Publications
Research SquareDec 2024 DOI:
10.21203/rs.3.rs-5536951/v1

Discovery and language model-guided design of hyperactive transposase

Güell, Marc; Ivančić, Dimitrije; Agudelo, Alejandro; Lindstrom-Vautri, Jonathan; Jaraba-Wallace, Jessica; Gallo, Maria; Ragel, Alejandro; Higueras, Irene; Billeci, Federico; Sanvicente, Marta; Petazzi, Paolo; Ferruz, Noelia; Sánchez-Mejías, Avencia; Das, Ravi
Product Used
Genes
Abstract
The PiggyBac transposase gene writing system has been efficiently used across biotechnological applications, however its diversity and biochemical potential remain largely unexplored. By developing a eukaryotic transposon mining pipeline, we expand the known diversity by two orders of magnitude and experimentally validate a subset of highly divergent PiggyBacs. We then fine tune a protein language model to further expand PiggyBac sequence space and discover transposons with improved activity, compatible with T-cell engineering and Cas9-guided programmable transposition. Our work illustrates how combining bioprospecting and AI-driven sequence exploration can accelerate the discovery of novel eukaryotic gene writing tools.
Product Used
Genes

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