Evidence map›Paper›PMID 41056201›Full record

ArticleJCI insight2025

CRISPR/Cas-mediated activation of genes associated with inherited retinal dystrophies in human cells for diagnostic purposes.

Valentin J Weber, Alice Reschigna, Maximilian J Gerhardt, Thomas Heigl, Klara S Hinrichsmeyer, Sander van den Engel, Dina Y Otify, Zoran Gavrilov, Frank Blaser, Isabelle Meneau and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

15 authors.

Valentin J WeberLaboratory for Retinal Gene Therapy, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Alice ReschignaDepartment of Ophthalmology, LMU University Hospital, LMU Munich, Munich, Germany.
Maximilian J GerhardtDepartment of Ophthalmology, LMU University Hospital, LMU Munich, Munich, Germany.
Thomas HeiglLaboratory for Retinal Gene Therapy, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Klara S HinrichsmeyerLaboratory for Retinal Gene Therapy, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Sander van den EngelLaboratory for Retinal Gene Therapy, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Dina Y OtifyDepartment of Pharmacy - Center for Drug Research, LMU Munich, Munich, Germany.
Zoran GavrilovLaboratory for Retinal Gene Therapy, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Frank BlaserDepartment of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.
Isabelle MeneauDepartment of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.
Christian BetzBioscientia Human Genetics, Bioscientia Institute of Medical Diagnostics, Ingelheim, Germany.
Hanno J BolzBioscientia Human Genetics, Bioscientia Institute of Medical Diagnostics, Ingelheim, Germany.
Martin BielDepartment of Pharmacy - Center for Drug Research, LMU Munich, Munich, Germany.
Stylianos MichalakisDepartment of Ophthalmology, LMU University Hospital, LMU Munich, Munich, Germany.
Elvir BecirovicLaboratory for Retinal Gene Therapy, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many patients suffering from inherited diseases do not receive a genetic diagnosis and are therefore excluded as candidates for treatments, such as gene therapies. Analyzing disease gene transcripts from patient cells holds potential for detection and interpretation of causative variants, but may be complicated by unavailability of affected tissue and/or lack of expression of the respective genes in blood or other easily accessible tissues. Using CRISPR/Cas-mediated transcriptional activation (CRISPRa), we developed a robust and efficient approach to activate genes in skin-derived fibroblasts and in freshly isolated peripheral blood mononuclear cells (PBMCs) from healthy individuals. This approach was successfully applied to blood samples from patients with inherited retinal dystrophies (IRDs). We were able to efficiently activate several IRD genes and detect their transcript isoforms using different diagnostically relevant methods such as RT-(q)PCR and long- and short-read RNA sequencing. CRISPRa-mediated transcriptional activation in PBMCs and fibroblasts will contribute to closing the critical gap in the genetic diagnosis of patients with IRD or other inherited diseases.

Indexed as

CRISPR-Cas SystemsRetinal DystrophiesTranscriptional ActivationFibroblastsGene EditingHumansLeukocytes, MononuclearDiagnosticsGenetic diseasesGeneticsOphthalmologyRNA processing

Identifiers

PMID41056201
PMCPMC12643484

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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.