Uploaded July 2026 | Updated September 2026, 2 weeks ago
Base Editing (BE) is a form of CRISPR/Cas gene editing that uses nucleotide deaminases to alter single nucleotide bases (letters) in DNA sequences (make point changes). A guide RNA guides a modified Cas protein to a specific site in
DNA, which a protein attached to the Cas protein then modifies. A nickase Cas (nCas) protein cuts one strand to differentiate it, and a deaminase protein attached to the nCas removes an amine (NH3 group) from the targeted nucleotide, leading it to be reinterpreted. The cell "fixes" the nicked DNA through mismatch repair, and the other strand gets fixed in replication.
Here’s a walk/talk-through of the 2016 paper that introduced base editing to the world.
This paper introduced base editing with a cytosine base editor
Komor, A. C.; Kim, Y. B.; Packer, M. S.; Zuris, J. A.; Liu, D. R. Programmable Editing of a Target Base in Genomic DNA without Double-Stranded DNA Cleavage. Nature 2016, 533 (7603), 420–424. doi.org/10.1038/nature17946.
This paper introduced adenine base editing
Gaudelli, N. M.; Komor, A. C.; Rees, H. A.; Packer, M. S.; Badran, A. H.; Bryson, D. I.; Liu, D. R. Programmable Base Editing of A•T to G•C in Genomic DNA without DNA Cleavage. Nature 2017, 551 (7681), 464–471. doi.org/10.1038/nature24644.
This is a nice primer on base editing
Mawson, S. J.; Dunne-Dombrink, K. A.; Pollak, B. R.; Komor, A. C. Precision Genome Editing with DNA Base Editors. Nat Rev Methods Primers 2026, 6 (1), 23. doi.org/10.1038/s43586-026-00478-3.
A bit of context (from my past posts):
Making double stranded cuts in the DNA can kind of make the cell freak out. And it can also lead to changes you don't want like pieces of chromosomes getting switched, swapped and lots of things that could potentially even do, have outcomes like causing cancer if they're in the wrong place. And so the technology has kind of been moving away from this more conventional CRISPR/Cas.
So in the lab, it's great a lot of times. But if we want to use it for, say, therapeutics, we want something that's more precise, something that's more efficient and something that is we can make more a wider range of edits–introduce the Cas nickases! (nCas proteins).Nickases only cut one strand of DNA. Cas proteins can be turned into nickases by inactivating one of the 2 catalytic sites (the HNH or RuvC domain). Depending on which you inactivate, you’ll cut the strand that the guide binds to, or cut the opposite strand.
nCas proteins are typically attached (“conjugated”) to another protein, an enzyme that's going to actually do something to modify the DNA. Because like if you make one strand, the cell's just like, okay, I'll just sit your back up. No big deal. But if you have something that modifies the DNA when you cut it, then you can kind of have a way to introduce changes that you want.
There are two main forms of this that are typically used. There's base editing (BE) and prime editing (PE).
Base editing. What it does is it uses base modifiers (typically nucleotide deaminases) to alter single nucleotides to make point changes.
And so what this allows you to do is say, in the case of an adenine base editor, you would deaminate the adenine. That would give you hypoxanthine, which is the base for inosine that gets red as guanine. If you have cytosine and then you deaminate it, you get your cell and then in your cell, that is going to be read as thymine. And then the opposite strand, you're going to get an adenine. And so you get both strands changed. And if you want to learn more about that I recommend the adgene blog. There are also versions, newer versions where you can also do other changes. So in addition to transitions you can do transversions.
You might be wondering why not just use a catalytic like dead cast protein for this? Why do you actually need to snip the DNA? A couple reasons one, with the catalytic, the CAS proteins, there's less specificity because the requirements for actually cutting are going to be stricter than the requirements for binding, which is why you can get more off target effects with the dead CAS proteins.
Also, by making that net, you're kind of differentiating the two strands. And so you have the next strand that the is going to be like oh that's the damaged strand. So I'm going to use the strand that was just edited as a template for fixing that other strand.
Base editors are great if you just want to make a single change. So if you're trying to correct like a point mutation, maybe the patient only has a single a single nucleotide that's wrong in their gene. Voila. Let's go in and fix it. But if you want a bigger change, say you want to make a large insertion or deletion? Well here you want to use something else. Introducing prime editing.
Finished in comments
Base Editing (BE) is a form of CRISPR/Cas gene editing that uses nucleotide deaminases to alter single nucleotide bases (letters) in DNA sequences (make point changes). A guide RNA guides a modified Cas protein to a specific site in
DNA, which a protein attached to the Cas protein then modifies. A nickase Cas (nCas) protein cuts one strand to differentiate it, and a deaminase protein attached to the nCas removes an amine (NH3 group) from the targeted nucleotide, leading it to be reinterpreted. The cell "fixes" the nicked DNA through mismatch repair, and the other strand gets fixed in replication.
Here’s a walk/talk-through of the 2016 paper that introduced base editing to the world.
This paper introduced base editing with a cytosine base editor
Komor, A. C.; Kim, Y. B.; Packer, M. S.; Zuris, J. A.; Liu, D. R. Programmable Editing of a Target Base in Genomic DNA without Double-Stranded DNA Cleavage. Nature 2016, 533 (7603), 420–424. doi.org/10.1038/nature17946.
This paper introduced adenine base editing
Gaudelli, N. M.; Komor, A. C.; Rees, H. A.; Packer, M. S.; Badran, A. H.; Bryson, D. I.; Liu, D. R. Programmable Base Editing of A•T to G•C in Genomic DNA without DNA Cleavage. Nature 2017, 551 (7681), 464–471. doi.org/10.1038/nature24644.
This is a nice primer on base editing
Mawson, S. J.; Dunne-Dombrink, K. A.; Pollak, B. R.; Komor, A. C. Precision Genome Editing with DNA Base Editors. Nat Rev Methods Primers 2026, 6 (1), 23. doi.org/10.1038/s43586-026-00478-3.
A bit of context (from my past posts):
Making double stranded cuts in the DNA can kind of make the cell freak out. And it can also lead to changes you don't want like pieces of chromosomes getting switched, swapped and lots of things that could potentially even do, have outcomes like causing cancer if they're in the wrong place. And so the technology has kind of been moving away from this more conventional CRISPR/Cas.
So in the lab, it's great a lot of times. But if we want to use it for, say, therapeutics, we want something that's more precise, something that's more efficient and something that is we can make more a wider range of edits–introduce the Cas nickases! (nCas proteins).Nickases only cut one strand of DNA. Cas proteins can be turned into nickases by inactivating one of the 2 catalytic sites (the HNH or RuvC domain). Depending on which you inactivate, you’ll cut the strand that the guide binds to, or cut the opposite strand.
nCas proteins are typically attached (“conjugated”) to another protein, an enzyme that's going to actually do something to modify the DNA. Because like if you make one strand, the cell's just like, okay, I'll just sit your back up. No big deal. But if you have something that modifies the DNA when you cut it, then you can kind of have a way to introduce changes that you want.
There are two main forms of this that are typically used. There's base editing (BE) and prime editing (PE).
Base editing. What it does is it uses base modifiers (typically nucleotide deaminases) to alter single nucleotides to make point changes.
And so what this allows you to do is say, in the case of an adenine base editor, you would deaminate the adenine. That would give you hypoxanthine, which is the base for inosine that gets red as guanine. If you have cytosine and then you deaminate it, you get your cell and then in your cell, that is going to be read as thymine. And then the opposite strand, you're going to get an adenine. And so you get both strands changed. And if you want to learn more about that I recommend the adgene blog. There are also versions, newer versions where you can also do other changes. So in addition to transitions you can do transversions.
You might be wondering why not just use a catalytic like dead cast protein for this? Why do you actually need to snip the DNA? A couple reasons one, with the catalytic, the CAS proteins, there's less specificity because the requirements for actually cutting are going to be stricter than the requirements for binding, which is why you can get more off target effects with the dead CAS proteins.
Also, by making that net, you're kind of differentiating the two strands. And so you have the next strand that the is going to be like oh that's the damaged strand. So I'm going to use the strand that was just edited as a template for fixing that other strand.
Base editors are great if you just want to make a single change. So if you're trying to correct like a point mutation, maybe the patient only has a single a single nucleotide that's wrong in their gene. Voila. Let's go in and fix it. But if you want a bigger change, say you want to make a large insertion or deletion? Well here you want to use something else. Introducing prime editing.
Finished in comments
