Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice [genomicDNA]

ABSTRACT: We assessed genome editing strategies to treat cardiomyopathy in mice including one or two doses of ABE8e, or one low, medium, or high dose of SaCas9 nuclease We conducted RNA analysis and genomic DNA analysis at the target region and transcriptome-wide analysis to assess cellular phenotypes

ORGANISM(S): Mus musculus

PROVIDER: GSE220850 | GEO | 2022/12/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Efficient in vivo Genome Editing Prevents Hypertrophic Cardiomyopathy in Mice [Amplified_cDNA]

Project description:Dominant pathogenic variants encoding amino acid substitutions in cardiac myosin heavy chain cause hypertrophic cardiomyopathy (HCM), a currently incurable disorder that increases risk for stroke, heart failure, and sudden cardiac death. We assessed the efficacy of two different genetic therapies, an adenine base editor (ABE8e) and a potent Cas9 nuclease delivered by AAV9, to prevent disease in mice carrying the heterozygous HCM pathogenic variant myosin R403Q. One dose of dual AAV9 vectors, each carrying one half of RNA-guided ABE8e, corrected the pathogenic variant in ≥70% of ventricular cardiomyocytes and maintained durable, normal cardiac structure and function. An additional dose provided more global editing especially in the atria but also increased bystander editing. AAV9 delivery of RNA-guided Cas9 nuclease effectively inactivated the pathogenic allele, albeit with dose-dependent toxicities, necessitating a narrow therapeutic window to maintain health. These preclinical studies demonstrate considerable potential for single-dose genetic therapies to correct or silence pathogenic variants and prevent the development of HCM.

2022-12-13 | GSE220811 | GEO

Efficient in vivo Genome Editing Prevents Hypertrophic Cardiomyopathy in Mice [Nuc-Seq]

2022-12-13 | GSE220808 | GEO

Efficient in vivo Genome Editing Prevents Hypertrophic Cardiomyopathy in Mice [RNA-seq]

2022-12-13 | GSE220517 | GEO

Base editing effectively prevents the early-onset hypertrophic cardiomyopathy in Mybpc3 mutant mice

Project description:Pathogenic variants in MYBPC3 (myosin-binding protein C3) are the leading cause of genetic hypertrophic cardiomyopathy (HCM). Currently, there is no specific and effective treatment for this disease. Base editing is an emerging modality for treating monogenic diseases; however, its effect on MYBPC3 cardiomyopathy remains unexplored. Mybpc3-R946X/R946X mice developed early-onset left ventricular hypertrophy, systolic dysfunction, ventricular dilatation, and arrythmias. SpRY-ABEmax inefficiently corrected the Mybpc3-R946X mutation. In contrast, SpRY-ABE8e increased the efficiency by 3.6-fold and retained low level off-target editing. In vivo administration of SpRY-ABE8e efficiently corrected Mybpc3-R946X mutation in cardiomyocytes and prevented heart function decline, hypertrophic cardiomyopathy, and ventricular dysfunction. The therapeutic efficacy of SpRY-ABE8e-mediated gene correction surmounted AAV-mediated Mybpc3 gene replacement.Our study unveiled the immense potential of base editing to treat fatal inherited cardiomyopathies and opened a new avenue for the therapeutic managements of inherited cardiac diseases.

2024-04-04 | GSE239872 | GEO

Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-13 | GSE220851 | GEO

Human Cardiac Proteome of Hypertrophic Cardiomyopathy

Project description:This study utilized TMT to characterize the cardiac proteomic differences between patients with hypertrophic cardiomyopathy and controls.

2023-04-28 | MSV000091821 | MassIVE

HipSci RNASEQ Hypertrophic Cardiomyopathy

Project description:The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNAseq on iPS lines from Hypertrophic Cardiomyopathy patients.

| EGAS00001001994 | EGA

Human hypertrophic cardiomyopathy cardiac tissue phosphoproteomics

Project description:This study used TMT-pro method to look for phosphoproteomic differences in heart tissue of patients with hypertrophic cardiomyopathy and controls

2023-04-28 | MSV000091822 | MassIVE

MicroRNA Profiling of Surgical Myectomy Tissue from Patients with Hypertrophic Cardiomyopathy

Project description:Using a high-throughput gene expression profiling technology, we have illuminated novel potential microRNA (miRNA) components of the molecular disease process underlying human hypertrophic cardiomyopathy (HCM). It is hoped that this will fuel future research endeavors that will eventually uncover the role miRNAs may play in the phenotypic heterogeneity of the disease, and thus, provide potential tools for identifying patients with benign versus malignant forms of the disease. Case (n = 107)-Control (n=20) study comparing the microRNA transcriptome of cardiac tissues from patients with hypertrophic cardiomyopathy to the microRNA transcriptome of control donor cardiac tissues.

2012-09-01 | E-GEOD-36946 | biostudies-arrayexpress

Transcriptome Profiling of Surgical Myectomy Tissue from Patients with Hypertrophic Cardiomyopathy

Project description:Using a high-throughput gene expression profiling technology, we have been able to develop new hypotheses regarding the molecular pathogenic mechanisms of human hypertrophic cardiomyopathy (HCM). It is hoped that these hypotheses, among others generated by this data, will fuel future research endeavors that will uncover novel biomarkers, prognostic indicators, and therapeutic targets to improve our ability to diagnose, counsel, and treat patients with this highly heterogeneous and potentially life-threatening condition. Case-control study comparing the messenger RNA transcriptome of cardiac tissues from patients with hypertrophic cardiomyopathy to the transcriptome of control donor cardiac tissues.

2012-09-01 | E-GEOD-36961 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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