PE2

PE2 (Prime Editor 2) is a genome editing tool, the second version of the prime editing platform, designed to install precise base substitutions, insertions, and deletions in genomic DNA without introducing double-strand breaks.

In PE2, the editing system consists of a Cas9 nickase fused to a reverse transcriptase and a prime editing guide RNA (pegRNA) that encodes the desired edit. The Cas9 nickase creates a single-strand break in the target DNA, and the reverse transcriptase uses the pegRNA as a template to write the edit into the genome. PE2 uses an engineered reverse transcriptase to improve efficiency and fidelity over the first iteration.

PE2 is part of the prime editing family and differs from PE1 by the use of an enhanced reverse transcriptase; later variants such as PE3 recruit an additional nicking sgRNA to further improve editing efficiency, while PE4 and PE5 incorporate strategies to modulate DNA repair pathways.

Applications include editing in human cells and model organisms, with potential therapeutic applications for correcting pathogenic mutations. Limitations include variable editing efficiency across loci and cell types, delivery challenges, and concerns about off-target edits and unintended insertions. This method provides an alternative to double-strand-break–based approaches, offering precision with fewer indels. See also prime editing, CRISPR, pegRNA, and the PE3–PE5 variants in the prime editing lineage.