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Record W4410396192 · doi:10.1056/nejmoa2504747

Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease

2025· article· en· W4410396192 on OpenAlexaff
Kiran Musunuru, Sarah Grandinette, Xiao Wang, Taylor R. Hudson, Kevin Briseno, Anne Marie Berry, Julia Hacker, Alvin Hsu, Rachel A. Silverstein, Logan T. Hille, Nancy A. Robinson-Garvin, Juliana C. Small, Sarah McCague, Samantha Burke, Christina M. Wright, Sarah K. Bick, Venkata S.K. Indurthi, Shweta Sharma, Michael Jepperson, Christopher A. Vakulskas, Michael A. Collingwood, Kate Keogh, Ashley M. Jacobi, Morgan Sturgeon, Christian M. Brommel, Ellen Schmaljohn, Gavin Kurgan, Thomas F. Osborne, He Zhang, Kyle J. Kinney, Garrett R. Rettig, Christopher Barbosa, Sean C. Semple, Ying K. Tam, Cathleen Lutz, Lindsey A. George, Benjamin P. Kleinstiver, David R. Liu, Kim T. Ng, Sadik H. Kassim, Petros Giannikopoulos, Mohamad‐Gabriel Alameh, Fyodor D. Urnov, Rebecca C. Ahrens‐Nicklas

Bibliographic record

VenueNew England Journal of Medicine · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsAcuitas Therapeutics (Canada)
FundersNational Center for Advancing Translational SciencesNational Institute of Neurological Disorders and StrokeNational Heart, Lung, and Blood InstituteNIH Office of the DirectorNational Cancer InstituteNational Institutes of HealthChildren's Hospital of Philadelphia
KeywordsGenome editingIn vivoGeneRare diseaseDiseaseMedicineGeneticsBiologyComputational biologyBioinformaticsPathologyCRISPR

Abstract

fetched live from OpenAlex

Base editors can correct disease-causing genetic variants. After a neonate had received a diagnosis of severe carbamoyl-phosphate synthetase 1 deficiency, a disease with an estimated 50% mortality in early infancy, we immediately began to develop a customized lipid nanoparticle-delivered base-editing therapy. After regulatory approval had been obtained for the therapy, the patient received two infusions at approximately 7 and 8 months of age. In the 7 weeks after the initial infusion, the patient was able to receive an increased amount of dietary protein and a reduced dose of a nitrogen-scavenger medication to half the starting dose, without unacceptable adverse events and despite viral illnesses. No serious adverse events occurred. Longer follow-up is warranted to assess safety and efficacy. (Funded by the National Institutes of Health and others.).

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Case report · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.005
GPT teacher head0.268
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designCase report
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations278
Published2025
Admission routes1
Has abstractyes

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