Evidence map›Paper›PMID 33513359›Full record

ArticleStem cell reports2021

Gene Therapy of Dominant CRX-Leber Congenital Amaurosis using Patient Stem Cell-Derived Retinal Organoids.

Kamil Kruczek, Zepeng Qu, James Gentry, Benjamin R Fadl, Linn Gieser, Suja Hiriyanna, Zachary Batz, Mugdha Samant, Ananya Samanta, Colin J Chu and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 2% of its field
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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
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  10. Review
  11. PreclinicalbioRxiv : the preprint server for biology · 2026
    Article
  12. Article
  13. Article
  14. International journal of molecular sciences · 2025
    Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Cone Rod Homeobox (Ophthalmic genetics · 2025
    Review
  20. Article

7 more citing papers are in PubMed but not listed here.

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

14 authors at 2 institutions in 1 country.

Kamil KruczekNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Zepeng QuNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
James GentryNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Benjamin R FadlNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Linn GieserNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Suja HiriyannaOcular Gene Therapy Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Zachary BatzNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Mugdha SamantNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Ananya SamantaOcular Gene Therapy Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Colin J ChuLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Laura CampelloNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Brian P BrooksOphthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Zhijian WuOcular Gene Therapy Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Anand SwaroopNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA. Electronic address: swaroopa@nei.nih.gov.
National Eye Institute · USNational Institutes of Health · US

Funding

Regulation of retinal developmentZIAEY000450 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2009 to 2025
$71.0M
Mechanisms, modeling and therapies of retinal and macular neurodegenerationZIAEY000546 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2015 to 2025
$36.3M
Intramural NIH HHS ZIA EY000450Intramural NIH HHS ZIA EY000546
6 · The paper itself

Abstract

Mutations in the photoreceptor transcription factor gene cone-rod homeobox (CRX) lead to distinct retinopathy phenotypes, including early-onset vision impairment in dominant Leber congenital amaurosis (LCA). Using induced pluripotent stem cells (iPSCs) from a patient with CRX-I138fs48 mutation, we established an in vitro model of CRX-LCA in retinal organoids that showed defective photoreceptor maturation by histology and gene profiling, with diminished expression of visual opsins. Adeno-associated virus (AAV)-mediated CRX gene augmentation therapy partially restored photoreceptor phenotype and expression of phototransduction-related genes as determined by single-cell RNA-sequencing. Retinal organoids derived from iPSCs of a second dominant CRX-LCA patient carrying K88N mutation revealed the loss of opsin expression as a common phenotype, which was alleviated by AAV-mediated augmentation of CRX. Our studies provide a proof-of-concept for developing gene therapy of dominant CRX-LCA and other CRX retinopathies.

Indexed as

AdultCell DifferentiationChildChild, PreschoolDependovirusFemaleGenetic TherapyHomeodomain ProteinsHumansInduced Pluripotent Stem CellsLeber Congenital AmaurosisModels, BiologicalMutationOpsinsOrganoidsPhenotypecone rod homeobox proteinHomeodomain ProteinsOpsinsTrans-Activators3-D organoidsAAVdisease modelingiPSCpluripotent stem cellsretinal degenerationscRNA-seqtherapytranscription factortranscriptome

Identifiers

PMID33513359
PMCPMC7878833
OpenAlexW3124056521

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.