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TRU-PE: A Universal, Trackable Prime Editor Toolkit for Robust Single- and Multi-Locus Genome Engineering

Qiu, Z.; Sun, K.; Zeng, Q.; Luo, Z.; Liu, X.; Li, Y.; Lei, X.; Zhao, R.; Zhang, Z.; Yang, Y.; Wang, X.; Hashemi, E.; Romero-Moya, D.; Zhang, J. Z.; Wang, X.; Giorgetti, A.; Liang, Z.

2026-02-21 genetics
10.64898/2026.02.20.706938 bioRxiv
Show abstract

Prime editing (PE) holds immense promise for precise genome editing, but its wider adoption is constrained by large payloads and inefficient delivery in recalcitrant cell types. Here, we present TRU-PE (Trackable, Robust, and Universal Prime Editor), a toolkit that overcomes these barriers via a split-vector architecture coupled with fluorescence-guided enrichment. This design ensures stoichiometric component expression, yielding marked improvements in editing efficiency and accelerated workflows compatible with both plasmid and viral delivery. By integrating a polycistronic hCtRNA-sgRNA/pegRNA array, the derivative TRU-MPE system enables simultaneous editing of up to ten genomic loci. Furthermore, it enhances the performance of evolved PE editors, allows flexible vector stoichiometry and inspires novel editing reporters. Leveraging these capabilities, we successfully generated a combinatorial human iPSC-based platform for GATA2 deficiency, which accurately recapitulates genotype-specific hematopoietic defects. TRU-PE thus provides a user-friendly, scalable framework for robust single- and multi-locus genome engineering, accelerating functional genomics and therapeutic development.

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The top 6 journals account for 50% of the predicted probability mass.

1
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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.