PE2 is an artificial 'prime editor' that can be used to introduce a desired change into the genome when complexed with a prime editing guide RNA (pegRNA) that specifies both the target site in the genome and also encodes the desired edit. PE2 is composed of a 'nickase' mutant form of the Streptococcus pyogenes Cas9 gene (contains a H840A amino acid substitution in the HNH domain), fused to an engineered form of the reverse transcriptase from the Moloney murine leukemia virus (contains amino acid substitutions D200N, L603W, T330P, T306K and W313F, which improve editing efficiency). The exact sequence may differ depending on the particular transgene or modified endogenous locus being used, for example, the coding sequence may have been codon optimized for use in different species and a nuclear localization signal may have been added. PE2 is targeted to a genomic target site of interest via guide RNA sequence within the pegRNA, where the Cas9(H840A) nickase makes a single strand break in the protospacer adjacent motif (PAM)-containing DNA strand. The 3' end of the nicked DNA strand can bind the pegRNA (due to the presence of a primer binding site within it), and the reverse transcriptase domain of PE2 can then reverse transcribe the desired edit from the pegRNA template into the genome. PE2 and a pegRNA can also be used in combination with an sgRNA designed to induce PE2 to nick the non-edited genome DNA strand, in a strategy called the 'Prime editor 3' (PE3) system; this approach can bias mismatch repair and has been shown to increase editing efficiency in mammalian cells (PMID:31634902).