Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CRISPR-free RNA Base Editing Mediated PTC-readthrough Restores Hearing in Mice with Otof Nonsense Mutation

ABSTRACT: We then deliver the ‘RESTART v3’ system, which is a CRISPR-free RNA base editor for nonsense mutation suppression, into the cochlea of the mice. We achieve physiological otoferlin expression, the edited premature termination codon is reverse-mutated to the original amino acid. We observe significant hearing restoration and enhancement of the behavioral auditory startle reflex.

ORGANISM(S): Homo Sapiens

SUBMITTER: Chengqi Yi

PROVIDER: PXD070139 | iProX | Fri Oct 31 00:00:00 GMT 2025

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

CRISPR-free RNA Base Editing Mediated PTC-readthrough Restores Hearing in Humanized Mice with Otof Nonsense Mutation [PRAISE]

Project description:Today, the gene editing for hereditary deafness is becoming a promising field with global interest. Among them, AAV-mediated otoferlin overexpression is undoubtedly the most successful representative of deaf-related gene therapy. However, it remains challenging to realize physiological, endogenous pattern of otoferlin expression. Here, we firstly generated a humanized homology Otof c.1315C>T (p.R439X), equivalent to OTOF c.1273C>T (p.R425X) identified in human with profound hearing loss, nonsense mutation-caused deaf mice model. We then delivered the ‘RESTART v3’ system, which is a CRISPR-free RNA base editor for nonsense mutation suppression, into the cochlea of the mice model. We accomplished a physiological manner of otoferlin expression; moreover, the edited premature termination codon is precisely reversed back to the original amino acid. Using multiple assays to estimate hearing restoration, we identified a significant reduced thresholds of auditory brain response (ABR) and statistical enhanced amplitudes of behavioral auditory startle reflex (ASR) in the treated mice with the RNA editing system. Thus, our study presented a successful CRISPR-free RNA editing approach to significantly restore hereditary deafness carrying humanized Otof c.1315C>T (p.R439X) non-sense mutation, providing a great promise for future clinical translation.

2025-10-27 | GSE262204 | GEO

CRISPR-free RNA Base Editing Mediated PTC-readthrough Restores Hearing in Humanized Mice with Otof Nonsense Mutation [TargetSeq]

2025-10-27 | GSE262206 | GEO

CRISPR-free RNA Base Editing Mediated PTC-readthrough Restores Hearing in Humanized Mice with Otof Nonsense Mutation [RNA-seq]

2025-10-27 | GSE262205 | GEO

Base editing improvement

Project description:Base editing improvement

| PRJNA598586 | ENA

Bimodal Adenine and Cytosine CRISPR Base Editing on DNA

Project description:Adenine and cytosine base editors (ABEs and CBEs) represent a new genome editing technology that allows the programmable installation of A-to-G or C-to-T alterations on DNA. We engineered Streptococcus pyogenes Cas9-based adenine and cytosine base editor (SpACE) that enables efficient simultaneous introduction of A-to-G and C-to-T substitutions in the same base editing window on DNA.

2020-07-02 | GSE137411 | GEO

PAM-flexible adenine base editing rescues hearing loss in a humanized MPZL2 mouse model harboring an East Asian founder mutation

Project description:Hearing loss is one of the most prevalent sensory disorders, but no commercial biological treatments are currently available. Here, we identify an East Asia-specific founder mutation, the homozygous c.220C>T mutation in MPZL2, that contributes to a significant proportion of hereditary deafness cases in our cohort study. We find that the disease-causing mutation can be targetable by adenine base editors (ABEs) that enable A·T-to-G·C base corrections without DNA double-strand breaks. To demonstrate this, we develop a humanized mouse model (hMPZL2Q74X/Q74X) that recapitulates human MPZL2 deafness and leads to progressive hearing loss. A PAM-flexible ABE variant with reduced bystander and off-target effects (ABE8eWQ-SpRY:sgRNA3) is packaged in dual adeno-associated viruses (AAVs) and injected into the inner ear of hMPZL2Q74X/Q74X mice and effectively corrects the mutation. This treatment significantly restores hearing function, improves inner ear structural integrity, and reverses altered gene expression. Base editing may hold therapeutic potential for hereditary deafness, including most cases of MPZL2 deafness.

2025-07-01 | GSE299064 | GEO

Heart-specific gene silencing via single-AAV-delivered base editing [RNA-Seq]

Project description:We used an adenine base editor to target the translation start site and mRNA splicing site of Camk2d in order to knock out CaMKIIδ. We found that editing the 5' splice site of intron 7 can lead to premature translation termination, effectively knocking out CaMKIIδ.

2025-01-21 | GSE265935 | GEO

Heart-specific gene silencing via single-AAV-delivered base editing [Amplicon-Seq]

2025-01-21 | GSE266652 | GEO

Base editing improvement

Project description:We examined the off-targets of new base editing tools at RNA level

2020-10-14 | GSE142840 | GEO

In vivo CRISPR base editing for treatment of Huntington’s disease

Project description:Huntington's disease (HD) is an inherited and ultimately fatal neurodegenerative disorder caused by an expanded polyglutamine-encoding CAG repeat within exon 1 of the huntingtin (HTT) gene, which produces a mutant protein that destroys striatal and cortical neurons. A potentially critical event in the pathogenesis of HD is the proteolytic cleavage of the mutant HTT protein, which leads to fragments of the N-terminal domain of the protein that form toxic aggregates. Given the role that proteolysis of the mutant HTT protein plays in HD, strategies for preventing this process hold potential for treating the disorder. By screening >1401 CRISPR base editors targeting splice elements in the HTT gene, we identify platforms capable of producing HTT protein isoforms resistant to proteolysis via the disruption of the splice acceptor sequence for exon 13. When delivered to the striatum of an HD rodent model, these base editors induced efficient exon skipping and decreased the formation of the HTT protein fragments, which in turn reduced HTT protein aggregation, improved functional deficits and attenuated striatal and cortical atrophy. Collectively, these results illustrate the potential for CRISPR base editing to decrease the toxicity of the mutant HTT protein for HD.

2024-07-12 | GSE272134 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data