Evidence map›Paper›PMID 40777742›Full record

ReviewMolecular therapy. Nucleic acids2025

Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges.

Nechama Kalter, Carla Fuster-García, Alfredo Silva, Víctor Ronco-Díaz, Stefano Roncelli, Giandomenico Turchiano, Jan Gorodkin, Toni Cathomen, Karim Benabdellah, Ciaran Lee and 1 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 2 pooled it
–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

48 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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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

11 authors.

Nechama KalterThe Institute for Advanced Materials and Nanotechnology, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
Carla Fuster-GarcíaInstitute for Transfusion Medicine and Gene Therapy, Medical Center-University of Freiburg, 79106 Freiburg, Germany.
Alfredo SilvaSan Raffaele Telethon Institute for Gene Therapy, Novel Gene Therapy Strategies Unit, 20132 Milan, Italy.
Víctor Ronco-DíazDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), 18016 Granada, Spain.
Stefano RoncelliCenter for Non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.
Giandomenico TurchianoInfection, Immunity, and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Jan GorodkinCenter for Non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.
Toni CathomenInstitute for Transfusion Medicine and Gene Therapy, Medical Center-University of Freiburg, 79106 Freiburg, Germany.
Karim BenabdellahDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), 18016 Granada, Spain.
Ciaran LeeSchool of Biochemistry and Cell Biology, University College Cork, T12 YN60 Cork, Ireland.
Ayal HendelThe Institute for Advanced Materials and Nanotechnology, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeted nucleases, primarily CRISPR-Cas-based systems, have revolutionized genome editing by enabling precise modification of target genes or transcripts. Many pre-clinical and clinical studies leverage this technology to develop treatments for human diseases; however, substantial off-target genotoxicity concerns delay its clinical translation. Despite the development of a wide array of tools, assays, and technologies aimed at identifying and quantifying off-target effects, the absence of standardized guidelines leads to inconsistent practices across studies. This review highlights the key challenges and potential solutions in ensuring the safety of gene editing studies for therapeutic applications, focusing on gRNA design, off-target sites prediction, and off-target activity measurement.

Indexed as

CRISPR-Cas9gene therapygenome editingMT: Clinical Applicationsoff-targetsafety

Identifiers

PMID40777742
PMCPMC12329535

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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.