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How does »Prime Editing« work ?

Since the gene-editing tool CRISPR-Cas9 has first emerged, it has proven a powerful tool. However, its lack of precision, the fact it is prone to errors and unintended effects, severely limits its ability to treat human genetic disease.

The popular CRISPR-Cas9 system (pictured). Credit: Juan Gaertner/SPL

How does »Prime Editing« work ?

Prime editing writes new genetic information into a specified DNA site, using a catalytically impaired Cas9 endonuclease, fused to an engineered reverse transcriptase, programmed with a prime editing guide RNA (pegRNA) that both specifies the target site and encodes the desired edit.

Recently, researchers at MIT and Harvard have developed an alternative, offering greater control over genome edits, called »prime editing«. This advancement could be especially important for the development of new gene therapies. With improved precision, prime editing improves chances that researchers end up with only the edits they were hoping for, instead of relatively unpredictable results.

Researchers today still face great challenges to correct genetic variants contributing to disease efficiently and without excess byproducts. One of prime editing main advantes are the reduction of »off-target« effects, which are a problematic issue with CRISPR-Cas9 applications. The use of a more stable approach, breaking only one of the two DNA strands, followed by specific changes only at the point of the cut, makes techniques using prime-editing approaches safer for use in human medicine. Additionally, the cell's own DNA repair system is removed from the equation, dramatically reducing risk of unpredictable results.

It is believed that prime editing has the potential to play a crucial role in the correction of 89% of the 75 thousand human genetic mutations, which are currently known to cause mutations. However, as promising as prime editing currently looks, it seems that the future of gene editing is likely to combine the use of several different techniques for different targeted treatments.

By Simon Fekonja, FAS Kemomed

You can read more about it in Nature.


Anzalone, A. V. et al. Nature (2019).

Ledford L. Nature 574, 464-465 (2019) doi: 10.1038/d41586-019-03164-5

Komor, A. C. et al. Nature 533, 420-424 (2016).

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