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categories: ["genetics"]categories: ["genetics"]tags: ["crispr", "genome editing", "gene therapy", "reverse transcriptase", "biotechnology"]tags: ["crispr", "genome editing", "gene therapy", "reverse transcriptase", "biotechnology"]summary: "A genome editing method in which a nicking Cas9 fused to a reverse transcriptase writes a new DNA sequence specified by an extended guide RNA."summary: "A genome editing method in which a nicking Cas9 fused to a reverse transcriptase writes a new DNA sequence specified by an extended guide RNA."updated: "2026-07-27"updated: "2026-08-23"humanEvidence: "Human use is one ex vivo trial in chronic granulomatous disease, which reported restored immune-cell function in a treated patient in 2025; in vivo correction has been shown only in mice."humanEvidence: "Human use is one ex vivo trial in chronic granulomatous disease, which reported restored immune-cell function in a treated patient in 2025; in vivo correction has been shown only in mice."access: "Not obtainable as a therapy: no prime editing product is approved anywhere as of 2026 and human use is confined to early-phase trials; the reagents are sold for research."access: "Not obtainable as a therapy: no prime editing product is approved anywhere as of 2026 and human use is confined to early-phase trials; the reagents are sold for research."reversibility: "irreversible"reversibility: "irreversible"issues: ["The 2025 chronic granulomatous disease result is stated without a citation."]------ ```infobox```infoboxlines 66–73 → 65–7747 unchanged lines not shown
Prime editing is a standard research tool for installing precise variants in cell lines, [[induced-pluripotent-stem-cells]] and [[organoids]], where the ability to write an exact patient mutation makes disease modelling far cleaner than nuclease-based approaches allow. In animals, prime editing has corrected the causal mutation in mouse models of metabolic liver disease and several other monogenic conditions, in each case in mice rather than in humans.[^bock2022]Prime editing is a standard research tool for installing precise variants in cell lines, [[induced-pluripotent-stem-cells]] and [[organoids]], where the ability to write an exact patient mutation makes disease modelling far cleaner than nuclease-based approaches allow. In animals, prime editing has corrected the causal mutation in mouse models of metabolic liver disease and several other monogenic conditions, in each case in mice rather than in humans.[^bock2022] Clinical translation began recently. The first prime editing therapy to reach patients treats chronic granulomatous disease by correcting a mutation in blood stem cells outside the body; initial results reported in 2025 indicated restoration of the missing immune-cell function in a treated patient. The company behind it subsequently restructured and redirected effort toward liver targets, a reminder that in this field the binding constraint is often capital rather than biology. No prime editing product is approved anywhere as of 2026.Clinical translation began recently. The first prime editing therapy to reach patients treats chronic granulomatous disease by correcting a mutation in blood stem cells outside the body; initial results reported in 2025 indicated restoration of the missing immune-cell function in a treated patient.[^gori2026] The company behind it subsequently restructured and redirected effort toward liver targets, a reminder that in this field the binding constraint is often capital rather than biology. No prime editing product is approved anywhere as of 2026. > [!caution] How thin the human record is> The entire clinical evidence for prime editing is one trial with two participants, whose blood stem cells were edited outside the body and returned after busulfan conditioning; restored NADPH oxidase activity was maintained to six and four months at the last reported follow-up.[^gori2026]> No prime editor has been delivered inside a human body — every in vivo correction is still in mice, in liver and a small number of other tissues.> What would settle the platform's case is durability measured in years and a second indication, and as of 2026 neither exists. > [!note] Terminology> [!note] Terminology> "Search and replace" is the phrase from the original paper and is apt for the mechanism, but it invites a word-processor analogy that overstates reliability. There is no undo, no confirmation step, and no guarantee the replacement is installed in every cell.> "Search and replace" is the phrase from the original paper and is apt for the mechanism, but it invites a word-processor analogy that overstates reliability. There is no undo, no confirmation step, and no guarantee the replacement is installed in every cell. lines 103–108 → 107–11329 unchanged lines not shown
## References## References [^anzalone2019]: `paper` Anzalone, A. V. et al. "Search-and-replace genome editing without double-strand breaks or donor DNA." *Nature*, 2019. {The demonstrations are in cultured cells, mostly human cell lines; efficiencies in primary cells and in living tissue are generally much lower.}[^anzalone2019]: `paper` Anzalone, A. V. et al. "Search-and-replace genome editing without double-strand breaks or donor DNA." *Nature*, 2019. {The demonstrations are in cultured cells, mostly human cell lines; efficiencies in primary cells and in living tissue are generally much lower.}[^gori2026]: `paper` Gori, J. L. et al. "Prime Editing for p47phox-Deficient Chronic Granulomatous Disease." *New England Journal of Medicine*, 2026; published online December 2025. {Two participants, both conditioned with busulfan; adverse events were attributed to the conditioning rather than the editor, and follow-up at publication was six and four months.}[^chen2021]: `paper` Chen, P. J. et al. "Enhanced prime editing systems by manipulating cellular determinants of editing outcomes." *Cell*, 2021.[^chen2021]: `paper` Chen, P. J. et al. "Enhanced prime editing systems by manipulating cellular determinants of editing outcomes." *Cell*, 2021.[^bock2022]: `paper` Böck, D. et al. "In vivo prime editing of a metabolic liver disease in mice." *Science Translational Medicine*, 2022. {Mice, and in liver, the tissue current delivery vehicles reach most easily; the result does not by itself extend to other organs or to people.}[^bock2022]: `paper` Böck, D. et al. "In vivo prime editing of a metabolic liver disease in mice." *Science Translational Medicine*, 2022. {Mice, and in liver, the tissue current delivery vehicles reach most easily; the result does not by itself extend to other organs or to people.}[^yarnall2023]: `paper` Yarnall, M. T. N. et al. "Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases." *Nature Biotechnology*, 2023.[^yarnall2023]: `paper` Yarnall, M. T. N. et al. "Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases." *Nature Biotechnology*, 2023.removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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