# Baby KJ **Entity class:** Clinical case **Domain:** Personalized Gene Editing / Rare Disease **Doc Type:** Case Node **Maturity:** Established **Collection:** [[collections/Neurotech|Neurotech]] **Primary Sources:** *New England Journal of Medicine*, 15 May 2025 ## Definition **KJ Muldoon is the infant with severe carbamoyl-phosphate synthetase 1 (CPS1) deficiency who received the first personalized in vivo gene-editing therapy given to a human.** A [[wiki/Base Editing|base editor]] bound to a guide designed for his individual mutation was delivered by [[wiki/Lipid Nanoparticle|lipid nanoparticle]] in two doses at seven and eight months old, beginning 25 February 2025. The case was presented by Kiran Musunuru at the American Society of Gene and Cell Therapy meeting in New Orleans on 15 May 2025 and published the same day in the *New England Journal of Medicine*. ## Record | Item | Record | |---|---| | Condition | Severe CPS1 deficiency, a urea cycle disorder | | Therapy | Bespoke base editor plus patient-specific guide, lipid-nanoparticle delivery | | Dosing | First infusion 25 February 2025; second dose at eight months old | | Institutions | Children's Hospital of Philadelphia and the University of Pennsylvania | | Investigators | Rebecca Ahrens-Nicklas (CHOP) and Kiran Musunuru (Penn) | | Regulatory route | Single-patient expanded-access investigational new drug application, processed in about one week | | Outcome | Discharged from CHOP for the first time in his life on 3 June 2025, after a stay of roughly 307 days | | Publication | N Engl J Med 2025;392(22):2235-43, DOI 10.1056/NEJMoa2504747 | ## Why the case governs the trajectory The unit of therapy became one patient, which is a structural break with every prior drug-development model. The FDA built its [[wiki/Plausible Mechanism Framework|Plausible Mechanism Framework]] on this case as the model, and [[wiki/ARPA-H|ARPA-H]] funded the AEGIS consortium to build the same capability as infrastructure rather than as a single rescue. Musunuru's own framing is that the case is a first step toward treating a wide variety of rare genetic disorders; the register's reading is that practitioner advocacy shaping regulatory design is the ordinary mechanism by which capability becomes permitted. ## Open Questions - Long-term durability of the edit and the need for redosing. - How many patients reach the same route now that the framework exists. - Whether an umbrella protocol replaces the single-patient application as the standard vehicle. ## Research Inferences These entries translate the forward-looking register in [[research/Research Inferences|Research Inferences]] into ordinary wiki prose. The tier labels apply to the inference, not automatically to every factual anchor inside it. Proposed IDs above INF-0500 come from the 2026-10-23 cycle: [[research/Research Inferences Integration Report - 2026-10-23|Research Inferences Integration Report — 2026-10-23]] · [[research/Research Inferences Integration Audit - 2026-10-23|Research Inferences Integration Audit — 2026-10-23]]. - **INF-0326 — Established.** An infant with CPS1 deficiency received a bespoke base-editing therapy designed for his individual mutation, dosed in February 2025 — the first personalized in vivo gene-editing treatment in a human. The unit of therapy became one patient, which is a structural break with every prior drug development model. - **INF-0327 — Established.** A CHOP-and-Penn clinical-research pair designed, manufactured, and administered an individualized editing therapy inside a compressed timeline. The named individuals and their institutional pairing are the transfer mechanism by which bespoke editing became clinically real. - **INF-0328 — Established.** The FDA's February 2026 draft framework permits first-in-human studies for individualized genetic therapies on preclinical proof-of-concept and allows new targets under a single application. Regulatory throughput, not editing chemistry, was the binding constraint, and this guidance directly relaxes it. - **INF-0331 — Established.** Base editors change single nucleotides without breaks, addressing the largest class of pathogenic variants. Roughly 350 million people live with one of about 5,000 genetic diseases, many carrying mutations unique to an individual, which defines the addressable population of individualized editing. - **INF-0334 — Strongly indicated.** LNP delivery is non-viral and redosable, avoiding the anti-capsid immunity that limits AAV to a single administration. Redosability converts gene editing from a one-shot event into a repeatable clinical procedure, which is the property continuous genetic maintenance requires. ## Relationships - **technique:** [[wiki/Base Editing|Base Editing]]. - **delivery:** [[wiki/Lipid Nanoparticle|Lipid Nanoparticle]]. - **regulatory_consequence:** [[wiki/Plausible Mechanism Framework|Plausible Mechanism Framework]] (built on this case) · [[wiki/United States Food and Drug Administration|United States Food and Drug Administration]]. - **infrastructure_response:** [[wiki/ARPA-H|ARPA-H]] AEGIS consortium. - **platform_successor:** [[wiki/Prime Editing|Prime Editing]] umbrella protocol for seven urea cycle disorders. - **cluster_home:** [[wiki/Real-Time Genetic Repair|Real-Time Genetic Repair]]. - **ecosystem:** [[wiki/Neurotechnology Ecosystem|Neurotechnology Ecosystem]] · [[collections/Neurotech|Neurotech]]. ## Sources - [Patient-specific in vivo gene editing to treat a rare genetic disease — New England Journal of Medicine, 15 May 2025](https://doi.org/10.1056/NEJMoa2504747) - [World's first patient treated with personalized CRISPR gene editing therapy — Children's Hospital of Philadelphia](https://chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital) - [First human study shows potential of personalized gene editing treatments — NIH Common Fund](https://commonfund.nih.gov/news/first-human-study-shows-potential-personalized-gene-editing-treatments-wide-range-disorders) - [First personalized CRISPR gene editing therapy patient Baby KJ discharged — Inside Precision Medicine](https://www.insideprecisionmedicine.com/topics/precision-medicine/first-personalized-crispr-gene-editing-therapy-patient-baby-kj-discharged) As of 23 October 2026.