Skip to content
ContentLora

    Tip: press / anywhere to search.

    concept

    Personalized (bespoke) gene editing

    Also known as bespoke gene editing, N-of-1 gene editing, individualized gene editing, patient-specific gene editing

    Personalized gene editing means designing an editing therapy for a single patient's disease-causing variant. The first reported case, in 2025, was an infant with severe CPS1 deficiency who received a custom base editor delivered by lipid nanoparticles.[1][2] In February 2026 the FDA proposed a "plausible mechanism" framework for approving such individualized therapies.[3]

    Editor reviewedStrict sourcingUpdated Gene editing and gene therapyHealth and medicineLife sciences
    Key facts

    Most medicines are built for thousands of patients. Personalized gene editing reverses that. A team reads one patient’s mutation and builds an editor to correct it.[1] This page describes a single published case and the regulatory response. It is not medical advice.

    The first case

    In 2025, a team at Children’s Hospital of Philadelphia and Penn Medicine treated an infant with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency. This is a rare urea-cycle disorder. Within about six months, the team designed and manufactured a base-editing therapy for the child’s variant. It was delivered to the liver by lipid nanoparticles.[1] The first infusion came in late February 2025, with further doses in March and April.[4]

    The case was published in NEJM in May 2025. CPS1 deficiency has an estimated 50% mortality in early infancy. In the seven weeks after the first infusion, the infant tolerated more dietary protein and needed half the starting dose of a nitrogen-scavenger medicine. The report described no serious adverse events.[2] The work was funded by the NIH Somatic Cell Genome Editing program, other NIH grants and industry contributions.[5] The therapy was given through the single-patient expanded-access (compassionate use) pathway.[6]

    One year on

    In February 2026, a year after the first infusion, Children’s Hospital of Philadelphia reported that the child had tolerated all three infusions with no serious side effects. He handled more dietary protein, needed less nitrogen-scavenging medication and showed better ammonia control during childhood illnesses. The hospital said the treatment is not a cure.[7]

    Why it matters

    The case showed that an editor can be designed, made and given to one patient within months.[1] Prime editing was estimated to address up to 89% of known disease variants in principle.[8]

    From one patient to a platform

    That specific therapy will not work for anyone else, though the team says swapping the targeting component could address other liver-based genetic disorders.[6] In March 2026 researchers at CHOP, Penn Medicine and the Broad Institute described a reusable version in The American Journal of Human Genetics. It pairs a lipid nanoparticle carrying prime editor mRNA to the liver with an AAV supplying the guide RNAs. In preclinical work it corrected about 30 to 40% of copies of a disease-causing variant, above the roughly 10% the researchers consider necessary for clinical benefit.[9]

    The team is planning an umbrella Phase 1/2 trial under the FDA’s plausible mechanism framework. It would enroll patients with any of seven urea cycle disorders, each receiving a customized prime editor, and treat all the versions as one drug. The researchers say treating as few as 5 to 10 participants might support approval of the platform.[10]

    Regulation

    On 25 February 2026 the FDA published draft guidance on a “plausible mechanism” framework. It describes how to generate substantial evidence of effectiveness and safety for individualized therapies that target genetic conditions with a known biological cause. Public comments closed on 27 April 2026.[3] Two further draft guidances followed: one in April 2026 on next-generation sequencing for nonclinical off-target assessment, and one in June 2026 on the prior knowledge sponsors may draw on across editing programs.[11][12]

    Limits

    A single case cannot show how well, or how safely, the approach works in general.[2] Delivery remains a constraint: LNPs reach the liver well, but other organs remain hard to target.[13] The base-editing page covers the broader clinical pipeline.

    Questions readers ask

    Who was the first patient treated with a personalized gene-editing therapy?

    An infant with severe CPS1 deficiency, a rare urea-cycle disorder, treated at Children's Hospital of Philadelphia with a base editor designed for his specific variant. He received a first infusion in late February 2025 and further doses in March and April.[1][4]

    Did the personalized therapy work?

    The NEJM report described increased tolerance of dietary protein and a halved dose of nitrogen-scavenger medicine in the seven weeks after the first infusion, with no serious adverse events. This is a single case, so it cannot establish general efficacy.[2]

    How will regulators handle one-patient therapies?

    In February 2026 the FDA published draft guidance describing a plausible mechanism framework for generating evidence of safety and effectiveness for individualized therapies targeting genetic conditions with a known cause.[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]

      In 2025 a team at Children's Hospital of Philadelphia and Penn Medicine designed and manufactured, within about six months, a personalized base-editing therapy delivered by lipid nanoparticles to the liver for an infant with severe CPS1 deficiency, a rare urea-cycle disorder. confirmedas of 2026-10-10

    2. [2]

      The case was reported in NEJM in May 2025; CPS1 deficiency has an estimated 50% mortality in early infancy, and in the seven weeks after the first infusion the infant tolerated more dietary protein and half the starting dose of a nitrogen-scavenger medicine, with no serious adverse events. confirmedas of 2026-10-10

    3. [3]

      On 25 February 2026 the FDA published draft guidance on a "plausible mechanism" framework for generating evidence of effectiveness and safety for individualized therapies that target specific genetic conditions with a known biological cause; comments closed on 27 April 2026. confirmedas of 2026-10-10

    4. [4]

      The infant received a first infusion of the personalized therapy in late February 2025, followed by doses in March and April 2025. confirmedas of 2026-10-10

    5. [5]

      The personalized CPS1 therapy work was supported by grants from the NIH Somatic Cell Genome Editing program, other NIH funding and industry contributions. confirmedas of 2026-10-10

    6. [6]

      The infant treated in 2025 received his therapy through the single-patient expanded-access (compassionate use) pathway, and his team says that version of the therapy will not work for any other patient, although swapping the part that targets the genome could address other liver-centred genetic disorders. confirmedas of 2025-10-31

    7. [7]

      Children's Hospital of Philadelphia said in February 2026, one year after the first infusion, that the infant treated with the personalized CPS1 base editor had tolerated three infusions given from February through April 2025 with no serious side effects, handled more dietary protein, needed less nitrogen-scavenging medication and showed better ammonia control during childhood illnesses, and that the treatment is not a cure. confirmedas of 2026-02-24

    8. [8]

      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

    9. [9]

      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

    10. [10]

      The CHOP and Penn team behind the personalized CPS1 therapy is planning an umbrella Phase 1/2 trial under the FDA's plausible mechanism framework that would enroll patients with any of seven urea cycle disorders receiving customized prime editors, treating all versions as a single drug; the researchers say successful treatment of as few as 5 to 10 participants might be enough to support approval of the platform. confirmedas of 2026-03-30

    11. [11]

      On 15 April 2026 the FDA published draft guidance recommending next-generation sequencing methods for the nonclinical safety assessment of genome editing in human gene therapy products, with comments due by 14 July 2026. confirmedas of 2026-10-10

    12. [12]

      On 3 June 2026 the FDA published draft guidance on the prior knowledge that sponsors of ex vivo and in vivo genome-editing products may scientifically leverage to advance product development, with comments due by 1 September 2026. confirmedas of 2026-10-10

    13. [13]

      Lipid nanoparticles can carry Cas9 mRNA and guide RNA into tissues, but reliably targeting tissues other than the liver remains a challenge. confirmedas of 2026-10-10

    Revision history (2)
    1. Page created.
    2. Added the one-year update, the reusable urea-cycle prime-editing platform, the planned umbrella trial and two further FDA draft guidances.

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

    Cite this page

    "Personalized (bespoke) gene editing." ContentLora, updated Oct 10, 2026. https://contentlora.com/wiki/personalized-gene-editing

    Spotted an error? Suggest a correction or emailcorrections@contentlora.com.

    Keep exploring

    Connections
    Base editing UsesLipid nanoparticle … Delivered by
    ☰ Contents