ProPE, a modified form of prime editing, improved results for some DNA edits that conventional prime editing handled poorly in laboratory experiments. In a 2025 study, the researchers reported a 6.2-fold increase for edits that had achieved less than 5% efficiency with conventional prime editing, with the best result in that group reaching 29.3%. Those figures apply to the study’s tested edits—not to all genes or patients—and the work does not establish a treatment for people.
What ProPE changes about prime editing
Prime editing is a gene-editing approach designed to make targeted DNA changes. It uses a modified Cas9 protein fused to reverse transcriptase, together with a prime-editing guide RNA (pegRNA). The pegRNA directs the system to a DNA target and carries a template for the intended change.
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ProPE—short for “prime editing with a prolonged editing window”—adds a second guide RNA. This guide does not cut DNA; instead, it targets the reverse-transcriptase template near the intended edit. The authors report that this modification extends the range of positions where prime editing can work effectively.
What the 2025 study found
In the primary study by Sarah Laura Krausz and colleagues, published online in Nature Catalysis on October 10, 2025, ProPE improved editing for targets that had performed poorly with conventional prime editing. Among edits with less than 5% efficiency using conventional prime editing, the authors reported a 6.2-fold improvement, with efficiency reaching as high as 29.3% in the tested group. Read the study in Nature Catalysis.
The result is most relevant to the problem the method was designed to address: some targets are difficult to edit reliably with standard prime editing. A higher result at those targets is encouraging, but it does not mean every edit will improve by the same amount. Efficiency depends on the target and experimental setup.
How ProPE compares with conventional prime editing
| Comparison | Conventional prime editing | ProPE |
|---|---|---|
| Editing a low-performing target | In the study’s low-performing group, the included edits had less than 5% efficiency. | The authors reported a 6.2-fold improvement in that group, reaching up to 29.3%. |
| Editing-window range | The study describes the conventional editing window as more limited. | The authors report that ProPE expands the editing window, including edits beyond the typical prime-editing range. |
| Guide optimization | Prime editing can require extensive optimization, particularly of the pegRNA’s 3′ extension. | The authors report that their approach reduces the amount of optimization needed in the tested settings. |
| Evidence of use in people | The comparison in this paper is experimental, not a clinical demonstration. | The paper does not demonstrate a treatment in patients or establish clinical safety or benefit. |
The authors also report that ProPE broadened applicability to changes outside the typical prime-editing range, including a substantial portion of pathogenic single-nucleotide polymorphisms. That finding points to possible research uses; it does not show that those variants can be corrected safely or effectively in patients.
Independent reader supportYour contribution helps us test, update, and keep practical guides available for everyone.Why the result matters—and what remains unknown
Prime editing can be used to make substitutions, insertions and deletions, but therapeutic genome editing also faces broader challenges, including delivery and safety. Those are general issues for the field, not results established by the ProPE experiment. A review of prime editing and its wider context discusses the technology and challenges involved in moving genome editing toward therapeutic use.
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Krausz and colleagues identify disease modelling and future therapeutic intervention as potential applications. The study is preclinical research: it does not show that ProPE has treated a disease, works in patients, or is clinically safe. Its reported performance should be understood as evidence from the experimental settings tested by the authors.
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What to take away
- ProPE is a modification of prime editing, not a separate editing platform.
- Its added non-cutting guide RNA targets the reverse-transcriptase template near the intended edit.
- The strongest headline result applies to edits that performed below 5% with conventional prime editing: a reported 6.2-fold improvement, reaching up to 29.3% in the study’s tested group.
- The findings suggest a wider editing window and possible research applications, but do not establish a treatment or clinical benefit.
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