Evidence map›Paper›PMID 41923647›Full record

ReviewAmerican journal of human genetics2026

Implications of the FDA's new plausible mechanism framework for the development of a personalized in vivo prime editing platform.

Emily R Feierman, Madelynn N Whittaker, Aidan Quigley, Dominique L Brooks, Paige McVeigh, Angela X Nan, Alvin Hsu, Hooda Said, Ousamah Younoss Soliman, Ryan Giovenco and 6 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in American journal of human genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Emily R FeiermanCardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Metabolic Disease Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Madelynn N WhittakerCardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Aidan QuigleyCardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Dominique L BrooksCardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Paige McVeighMetabolic Disease Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Angela X NanCardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Alvin HsuBroad Institute of MIT and Harvard, Harvard University, Howard Hughes Medical Institute, Cambridge, MA 02139, USA.
Hooda SaidRaymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Ousamah Younoss SolimanRNA Technologies and Therapeutics Inc., Montreal, QC H2W 1R7, Canada.
Ryan GiovencoRaymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Beverly L DavidsonRaymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Mohamad-Gabriel AlamehDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
David R LiuBroad Institute of MIT and Harvard, Harvard University, Howard Hughes Medical Institute, Cambridge, MA 02139, USA.
Xiao WangCardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Kiran MusunuruCardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Metabolic Disease Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: kiranmusunuru@gmail.com.
Rebecca C Ahrens-NicklasMetabolic Disease Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: ahrensnicklasr@chop.edu.

Funding

Replication study of in vivo postnatal gene editing for metabolic liver disease in the nonhuman primate modelU19NS132301 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI Kiran Musunuru, William H. Peranteau · 2023 to 2026
$48.5M
Personalized prime editing as a platform for hepatic inborn errors of metabolismU01TR005355 · NCATS · CHILDREN'S HOSP OF PHILADELPHIA · PI Rebecca Clare Ahrens-Nicklas, Kiran Musunuru · 2024 to 2026
$10.8M
NCATS NIH HHS U01 TR005355NINDS NIH HHS U19 NS132301
6 · The paper itself

Abstract

In February 2026, the US Food and Drug Administration (FDA) published a draft guidance on a new plausible mechanism framework for the development and approval of individualized therapies for genetic conditions. Here, we report initial proof-of-concept studies supporting a customizable prime editing platform geared to the treatment of 7 urea cycle disorders (UCDs) and other liver-centered disorders, as well as the outcome of a formal meeting with the FDA to discuss the use of the platform in an "umbrella-of-umbrellas" clinical trial including subjects with any of the 7 UCDs. We anticipate our findings will be of interest to academic investigators and industry sponsors who wish to pursue expeditious FDA approvals of therapies for ultra-rare diseases using the plausible mechanism framework.

Indexed as

Gene EditingGenetic TherapyPrecision MedicineUrea Cycle Disorders, InbornHumansUnited StatesUnited States Food and Drug Administration

Identifiers

PMID41923647
PMCPMC13058825

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.