Evidence map›Paper›PMID 39922978›Full record

ArticleCommunications biology2025

Comparison of CRISPR-Cas13b RNA base editing approaches for USH2A-associated inherited retinal degeneration.

Lewis E Fry, Lauren Major, Ahmed Salman, Lucy A McDermott, Jun Yang, Andrew J King, Michelle E McClements, Robert E MacLaren

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Molecular therapy. Nucleic acids · 2025
    Review
  6. Multifaceted disruption of AMPA receptor signaling byComputational and structural biotechnology journal · 2025
    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

8 authors.

Lewis E FryNuffield Department of Clinical Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-0821-3954
Lauren MajorNuffield Department of Clinical Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Ahmed SalmanNuffield Department of Clinical Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4300-2033
Lucy A McDermottNuffield Department of Clinical Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Jun YangDepartment of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0002-4799-0465
Andrew J KingDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-5180-7179
Michelle E McClementsNuffield Department of Clinical Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-2941-4464
Robert E MacLarenNuffield Department of Clinical Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. maclaren@eye.ox.ac.uk.ORCID http://orcid.org/0000-0002-3096-4682

Funding

Disease mechanism of Usher syndrome 2R01EY034524 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jun Yang · 2023 to 2026
$1.8M
NEI NIH HHS R01 EY034524Wellcome Trust
6 · The paper itself

Abstract

CRISPR-Cas13 systems have therapeutic promise for the precise correction of point mutations in RNA. Using adenosine deaminase acting on RNA (ADAR) effectors, A-I base conversions can be targeted using guide RNAs (gRNAs). We compare the Cas13 effectors PspCas13b and Cas13bt3 for the repair of the gene USH2A, a common cause of inherited retinal disease and Usher syndrome. In cultured cells, we demonstrate up to 80% efficiency for the repair of the common c.11864 G > A and its murine equivalent c.11840 G > A, across different gRNAs and promoters. We develop and characterize a mouse model of Usher syndrome carrying the c.11840 G > A mutation designed for the evaluation of base editors for inherited retinal disease. Finally, we compare Cas13 effectors delivered via AAV for the repair of Ush2a in photoreceptors. Mean RNA editing rates in photoreceptors across different constructs ranged from 0.32% to 2.04%, with greater efficiency in those injected with PspCas13b compared to Cas13bt3 constructs. In mice injected with PspCas13b constructs, usherin protein was successfully restored and correctly localized to the connecting cilium following RNA editing. These results support the development of transcriptome targeting gene editing therapies for retinal disease.

Indexed as

CRISPR-Cas SystemsExtracellular Matrix ProteinsTargeted Gene RepairUsher SyndromesAdenosine DeaminaseAnimalsDependovirusHumansMice, Inbred C57BLMice, KnockoutPoint MutationRetinaRNA-Binding ProteinsRNA EditingTransgenesADARB1 protein, humanAdenosine DeaminaseExtracellular Matrix ProteinsRNA-Binding ProteinsUsh2a protein, mouse

Identifiers

PMID39922978
PMCPMC11807095

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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.