Prime editor: the rise of a new gene-editing superhero

River D'Almeida, Ph.D
3 min readMay 16, 2020
Prime Editing Superhero © Tara Fernandez

In a dark corner of the nucleus, a mutation lurks, up to no good. It stealthily swaps a DNA base — an A to a T — gleefully awaiting the catastrophic consequences on the encoded protein.

A brave CRISPR molecule enters the nucleus and armed with its razor sharp enzyme, Cas9, is determined to rid this genome of unwanted errors. Its other secret weapon, guide RNA, acts like a compass, directing CRISPR directly to the afflicted gene.

CRISPR launches a full-blown attack, hurling Cas9 at the faulty DNA strands in the hopes the cell patches up the mutations with the correct replacement sequence. As the dust settles, CRISPR realizes it has missed the mark — the cleaved section of the double helix was repaired incorrectly. The nefarious mutation wins this time.

All hope is not lost, however. A new superhero emerges, designed to pick up CRISPR’s slack and obliterate DNA glitches for good. Enter the prime editor. In a recent article published in Nature, inventors Andrew Anzalone and David Liu describe this game-changing gene editing innovation, pinning bold predictions on how this development can substantially surpass CRISPR’s mutation-busting abilities.

The team from Harvard University claims that prime editing has the capacity to mend a massive 89 percent of all the genetic mutations responsible for heritable human diseases.

What superpowers does prime editing hold that differentiate it from its predecessor?

Most of all, this new-and-improved system works with unrivalled precision and flexibility.

The standard approach of Cas9 is to snip both strands of DNA, relying completely on the cell’s notoriously inconsistent repair systems to reassemble them. This process is prone to errors, with the cell’s DNA repair machinery often inadvertently inserting or removing DNA bases at the cut site.

In prime editing, Cas9 gets a makeover, now only making one nick to a single strand to reduce the risk of mistakes. Directed by a guide RNA sequence, prime editing no longer relies on the cell’s repair system, but uses its own enzyme, reverse transcriptase, to make the necessary modifications.

River D'Almeida, Ph.D

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