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 [Nuc-Seq]

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

PROVIDER: PRJNA911594 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR22704557.fastq.gz	Fastqsanger.gz
	SRR22704558.fastq.gz	Fastqsanger.gz
	SRR22704559.fastq.gz	Fastqsanger.gz
	SRR22704560.fastq.gz	Fastqsanger.gz

Items per page:

1 - 4 of 4

Similar Datasets

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

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 | GSE220808 | GEO

Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice

Project description:Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice

| PRJNA911761 | ENA

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

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

| PRJNA911928 | ENA

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

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

| PRJNA911609 | ENA

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

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

| PRJNA910112 | ENA

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

2022-12-13 | GSE220811 | 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 [genomicDNA]

Project description: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

2022-12-13 | GSE220850 | GEO

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

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

| PRJNA1001311 | ENA