CRISPR is perhaps the most popular tool in the genome editing toolkit. However, despite CRISPR’s obvious success, there are concerns about double-stranded breaks leading to unwanted, potentially dangerous edits.1 At the same time, some applications might require larger changes than the fairly limited single-base substitution repertoire of base editors. Prime editing, which can achieve targeted edits with single-nucleotide precision and without cutting both strands of DNA, may offer a solution.
Since the inventors Andrew Anzalone and David Liu published their first report in 2019,2 they have developed a next-generation system, started a company, and released the first encouraging preclinical data. Now, prime editing is finally heading towards the ultimate goal: therapy.
Prime editing uses specialized machinery consisting of a prime editing guide RNA (pegRNA) and a Cas9 enzyme fused to a reverse transcriptase. The version of Cas9 used in prime editing has one of its two nuclease domains deactivated, turning ...


























