Base and prime gene editing

In plain language

Many early gene editing tools cut both strands of DNA and then rely on the cell to repair the break, which can leave unwanted changes. Base editors work differently. They pair a guide system, which finds a target spot in the genome, with an enzyme that changes one DNA letter (A, C, G or T) into another, without cutting through the double helix.

Prime editors, first described by Anzalone and colleagues in 2019, carry the new DNA sequence inside their guide and write it into the target site. This means they can make a wider range of changes than base editors can. Both approaches have so far been used mostly in cells, in animals and in a small number of people with rare inherited conditions.

Technical explanation

A typical base editor fuses a version of the CRISPR protein Cas9 that cannot cut both DNA strands to a deaminase enzyme. The deaminase removes an amino group from a base within a small window near the target, which changes how that base is read. Cytosine is changed so that it is read as thymine after repair and replication, and adenine as guanine, giving C-to-T and A-to-G edits. Rees and Liu (2018) review base-editing strategies and discuss developments that extend the scope, specificity, precision and in vivo delivery of base editors, along with their limitations.

Prime editing, described by Anzalone and colleagues (2019), uses a Cas9 nickase fused to a reverse transcriptase, guided by a prime editing guide RNA that contains both the target address and a template for the new sequence. The enzyme nicks one strand, copies the template onto it, and the cell's repair machinery then completes the change. The 2019 paper reports this as search-and-replace editing without double-strand breaks or donor DNA templates.

Delivery and off-target activity remain the main technical problems. Newby and colleagues (2021) report that ex vivo base editing of blood stem and progenitor cells from patients with sickle cell disease converted about 80% of the sickle allele. In mice that received the edited cells, the authors report near-normal haematological parameters, reduced splenic pathology and durable editing after secondary transplantation. In 2025, Musunuru and colleagues described one infant with severe CPS1 deficiency who was treated with a bespoke base-editing therapy delivered in lipid nanoparticles.

What the evidence says

Each statement is typed by the strength of its evidence and linked to the source that supports it.

Limitations and open problems

• Most published work is in cells, animals or a single patient, so the results from one case do not show how often the approach works.
• Common base editors make only certain changes; the deaminase enzymes mainly produce C-to-T and A-to-G edits, so other substitutions need different tools.
• Editing can also change nearby bases within the editing window (bystander edits), which has to be checked for each application.
• Delivery to the right tissue is hard. The 2025 case used lipid nanoparticles, and wider use will need methods that reach other organs.
• The 2025 report describes a therapy made for one patient. The sources reviewed here do not give costs or show that bespoke development can be repeated at scale.

Possible future uses

Timeline

1. 20 Apr 2016Komor and colleagues report programmable editing of a single target base in genomic DNA without double-stranded DNA cleavage. Sources: [1]
2. 15 Oct 2018Rees and Liu publish a review of base editing in Nature Reviews Genetics. Sources: [2]
3. 21 Oct 2019Anzalone and colleagues report search-and-replace (prime) genome editing without double-strand breaks or donor DNA. Sources: [3]
4. 2 Jun 2021Newby and colleagues report base editing of blood stem cells that rescues a sickle cell disease model in mice. Sources: [4]
5. 15 May 2025Musunuru and colleagues publish in the New England Journal of Medicine the treatment of one infant with CPS1 deficiency using a bespoke base-editing therapy. Sources: [5]

Futures this could help bring about

How far away?

AI-designed medicines reaching patients

Pilots · 5 of 8 steps done

How far away?

Curing inherited diseases with a single gene-editing treatment

Pilots · 4 of 9 steps done

Related breakthroughs

• Infant receives a base-editing therapy designed for his own mutation (15 May 2025)

Glossary

Base editor

A gene editing tool that changes one DNA letter into another at a target site, without cutting through both strands of the DNA.

Prime editor

A gene editing tool that uses a guide RNA carrying the new sequence to write a change into the target DNA, without a double-strand break.

Double-strand break

A cut through both strands of the DNA double helix, which the cell must repair.

Transition mutation

A change from one purine to another (A and G) or from one pyrimidine to another (C and T) in DNA.

Sources

1. peer reviewed paper
   Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
   Komor, Kim, Packer et al.. Nature, 20 Apr 2016. DOI: 10.1038/nature17946. Accessed 21 Oct 2026.
2. review articlecorrected
   Base editing: precision chemistry on the genome and transcriptome of living cells
   Rees, Liu. Nature Reviews Genetics, 15 Oct 2018. DOI: 10.1038/s41576-018-0059-1. Accessed 21 Oct 2026.
3. peer reviewed paper
   Search-and-replace genome editing without double-strand breaks or donor DNA
   Anzalone, Randolph, Davis et al.. Nature, 21 Oct 2019. DOI: 10.1038/s41586-019-1711-4. Accessed 21 Oct 2026.
4. peer reviewed paper
   Base editing of haematopoietic stem cells rescues sickle cell disease in mice
   Newby, Yen, Woodard et al.. Nature, 2 Jun 2021. DOI: 10.1038/s41586-021-03609-w. Accessed 21 Oct 2026.
5. peer reviewed paper
   Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease
   Musunuru K, Grandinette SA, Wang X et al.. New England Journal of Medicine, 15 May 2025. DOI: 10.1056/NEJMoa2504747. Accessed 21 Oct 2026.

Revision history

2 changes since this profile was created.