As a PhD student, I attended my first international scientific conference in October 2019. One of the keynote presentations was delivered by David R. Liu, who introduced prime editing, his group’s new precision genome-editing technology that enabled programmable rewriting of genomic DNA with unprecedented versatility. Just 2 weeks later, this work was published in Nature.

Before prime editing, CRISPR-based homology-directed repair was generally used for precise modification of genomic DNA. However, canonical Cas nucleases often induce double-strand breaks (DSBs) that lead to random insertions or deletions (indels). Base editing, another pioneering innovation from the Liu group, enables efficient C-to-T and A-to-G transitions without introducing DSBs but cannot support all 12 base substitutions or introduce targeted insertions and deletions. Prime editing overcomes these long-standing limitations through the use of a ‘search-and-replace’ mechanism that supports almost all classes of precise genomic modification.