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    Prime editing

    Also known as prime editor, PE, pegRNA editing

    Prime editing, first reported in 2019, uses an impaired Cas9, a reverse transcriptase and a special guide RNA to write insertions, deletions and any single-base change without double-strand breaks.[1] The first human data came in 2025, and its developer is working toward a first approval filing in the first half of 2027.[2][3]

    Editor reviewedStrict sourcingUpdated Gene editing and gene therapyLife sciencesHealth and medicine
    Key facts

    Prime editing extends crispr-cas9 from cutting to writing. Its developers presented it as able to correct, in principle, up to 89% of known disease-associated genetic variants.[4]

    How it works

    A prime editor joins a catalytically impaired Cas9 to an engineered reverse transcriptase. A prime editing guide RNA (pegRNA) both specifies the target and encodes the edit. In the 2019 paper this made targeted insertions, deletions and all 12 types of point mutation possible without double-strand breaks or donor DNA templates.[1] base-editing also avoids double-strand breaks, but makes direct base conversions rather than writing new sequence.[5]

    First clinical results

    In May 2025 Prime Medicine reported what it called the first clinical data supporting the safety and efficacy of prime editing in humans. The data came from PM359, an ex vivo prime-edited stem cell product for chronic granulomatous disease (CGD), an inherited immune disorder. DHR positivity, a measure of restored immune-cell function, reached 58% by day 15 and 66% by day 30. The company reported no serious adverse events related to PM359.[2] The results were published in NEJM in December 2025. Two participants with p47phox-deficient CGD received the therapy after busulfan conditioning. Neutrophils and platelets engrafted promptly in both, and NADPH oxidase activity appeared within a month and was maintained for six and four months respectively at last follow-up.[6]

    How it compares with other editors

    EditorWhat it doesDouble-strand break?
    Cas9 nucleaseCuts DNA at a guide-RNA-matched siteYes
    Base editorConverts one base into anotherNo
    Prime editorWrites insertions, deletions and all 12 single-base changes from a pegRNA templateNo

    Sources for the table: the original Cas9, base editing and prime editing papers.[7][5][1] Among these tools, only a Cas9 nuclease therapy, casgevy, had been approved as of October 2026.[8][3][9]

    Status in 2026

    • PM359 (CGD). The FDA granted Regenerative Medicine Advanced Therapy designation in June 2026. Prime Medicine is working toward a BLA submission in the first half of 2027.[3]
    • Wilson disease (PM577a). New Zealand’s Medsafe cleared the trial in June 2026 and the FDA cleared the US application in July 2026. It is Prime Medicine’s first in vivo prime-editing trial, with initial data expected in 2027.[10]
    • Alpha-1 antitrypsin deficiency (PM647). On 24 September 2026 the FDA cleared the trial application for PM647, which is designed to correct the Pi*Z mutation in SERPINA1. The Phase 1/2 study starts with adults who have lung-only disease and has initial data expected in 2027.[11]

    Prime editing inside the body

    Prime Medicine’s first two in vivo programs were cleared for trials in 2026. For alpha-1 antitrypsin deficiency, PM647 targets the Pi*Z mutation that the company says about 100,000 people in the US carry in the PiZZ form.[11][12] It enters a field where Beam’s BEAM-302 is already in a pivotal cohort.[13] In July 2026 an arbitration tribunal ruled that PM647 falls within Prime Medicine’s field under its 2019 agreement with Beam, that the company had not breached the agreement and that it owes no damages (company-reported).[14]

    Academic groups are also moving prime editing in vivo. In March 2026 researchers at CHOP, Penn Medicine and the Broad Institute reported a reusable prime-editing platform for urea cycle disorders, combining a lipid nanoparticle carrying editor mRNA with an AAV supplying guide RNAs.[15] See personalized-gene-editing.

    What to watch

    The human prime-editing data published so far come from the ex vivo PM359 program.[2] The Wilson disease and AATD trials, both with data expected in 2027, will be its first tests inside the body.[10][11] A first approval filing, for PM359, is planned for the first half of 2027.[3]

    Questions readers ask

    Why is prime editing called "search and replace"?

    Its guide RNA (pegRNA) both finds the target site and carries the new sequence, which a reverse transcriptase writes into the DNA, without a double-strand break or donor DNA.[1]

    Has prime editing been tested in people?

    Yes. In May 2025 Prime Medicine reported the first human data, from an ex vivo prime-edited stem cell therapy for chronic granulomatous disease, with 66% DHR-positive cells by day 30 and no serious adverse events related to the therapy.[2]

    When might a prime-editing therapy be approved?

    None is approved. Prime Medicine says it is working toward a BLA submission for PM359 in the first half of 2027; any approval would follow FDA review.[3]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      Prime editing, reported in Nature in 2019, pairs an impaired Cas9 with an engineered reverse transcriptase and a prime editing guide RNA (pegRNA) that both finds the target and encodes the edit, allowing insertions, deletions and all 12 kinds of single-base change without double-strand breaks or donor DNA. confirmedas of 2026-10-10

    2. [2]

      In May 2025 Prime Medicine reported the first clinical data for prime editing in humans, from PM359, an ex vivo prime-edited stem cell therapy for chronic granulomatous disease (CGD); the first patient reached 58% DHR-positive neutrophils by day 15 and 66% by day 30, with no serious adverse events related to PM359. confirmedas of 2026-10-10

    3. [3]

      The FDA granted PM359 Regenerative Medicine Advanced Therapy designation in June 2026, and Prime Medicine is working toward a BLA submission in the first half of 2027. confirmedas of 2026-08-06

    4. [4]

      The 2019 prime editing paper estimated that the method could in principle correct up to 89% of known disease-associated genetic variants. confirmedas of 2026-10-10

    5. [5]

      Base editing, reported in Nature in 2016, converts one DNA base into another in a programmable way without cutting both DNA strands, with typically 1% or fewer unwanted insertions or deletions in the original experiments. confirmedas of 2026-10-10

    6. [6]

      The PM359 results were published in NEJM in December 2025: two participants with p47phox-deficient chronic granulomatous disease received the prime-edited stem cell therapy after busulfan conditioning, neutrophils and platelets engrafted promptly in both, and NADPH oxidase activity appeared within one month and was maintained for six and four months respectively at last follow-up. confirmedas of 2025-12-07

    7. [7]

      A 2012 Science paper by Jinek, Doudna, Charpentier and colleagues showed that a two-RNA structure directs the Cas9 protein to make double-stranded breaks in target DNA, and highlighted its potential for RNA-programmable genome editing. confirmedas of 2026-10-10

    8. [8]

      On 8 December 2023 the FDA approved Casgevy, the first FDA-approved therapy using CRISPR/Cas9, for people aged 12 and older with sickle cell disease and recurrent vaso-occlusive crises. confirmedas of 2026-10-10

    9. [9]

      Beam plans to submit a Biologics License Application for risto-cel (formerly BEAM-101), a base-edited cell therapy for sickle cell disease, as early as year-end 2026. reportedas of 2026-08-04· forecast

    10. [10]

      New Zealand's Medsafe cleared Prime Medicine's trial application for the Wilson disease prime editor PM577a in June 2026, the company's first clinical authorization for an in vivo prime-editing therapy, and the FDA cleared its US investigational new drug application in July 2026, establishing a global open-label Phase 1/2 study with initial clinical data anticipated in 2027. confirmedas of 2026-08-06

    11. [11]

      On 24 September 2026 Prime Medicine said the FDA had cleared its investigational new drug application for PM647, an in vivo prime editor designed to correct the E342K (Pi*Z) mutation in SERPINA1; the global single-arm Phase 1/2 study will start with adults who have lung-only AATD and then add a cohort with significant liver disease, with initial clinical data expected in 2027. confirmedas of 2026-09-24

    12. [12]

      Prime Medicine says about 100,000 people in the United States carry the PiZZ genotype that PM647 is designed to correct, caused by the most prevalent disease-causing mutation in alpha-1 antitrypsin deficiency. confirmedas of 2026-09-24

    13. [13]

      In July 2026 Beam dosed the first patient in the global pivotal cohort of its BEAM-302 trial in AATD-associated lung disease. confirmedas of 2026-10-10

    14. [14]

      In July 2026 Prime Medicine announced a binding arbitration ruling under its 2019 collaboration agreement with Beam Therapeutics: the tribunal declared that PM647 is within Prime Medicine's defined field, that Prime Medicine did not breach the agreement and that it owes no monetary damages. confirmedas of 2026-08-06

    15. [15]

      In March 2026 researchers at Children's Hospital of Philadelphia, Penn Medicine and the Broad Institute reported in The American Journal of Human Genetics a customizable two-part in vivo prime-editing platform for urea cycle disorders - a lipid nanoparticle carrying editor mRNA to the liver plus an AAV supplying guide RNAs - that corrected about 30 to 40% of copies of a disease-causing variant in preclinical liver DNA, above the roughly 10% the researchers consider necessary for clinical benefit. confirmedas of 2026-03-30

    Revision history (2)
    1. Page created.
    2. Added the NEJM publication of PM359, the PM647 target population and Beam arbitration, and the academic urea-cycle prime-editing platform.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "Prime editing." ContentLora, updated Oct 10, 2026. https://contentlora.com/wiki/prime-editing

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