Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Brain-wide AAV-mediated silencing of prion protein by a compact epigenetic editor

ABSTRACT: Brain-wide AAV-mediated silencing of prion protein by a compact epigenetic editor

PROVIDER: PRJNA1077350 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR27991371_1.fastq.gz	Fastqsanger.gz
	SRR27991371_2.fastq.gz	Fastqsanger.gz
	SRR27991372_1.fastq.gz	Fastqsanger.gz
	SRR27991372_2.fastq.gz	Fastqsanger.gz
	SRR27991373_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 30

Similar Datasets

Brain-wide AAV-mediated silencing of prion protein by a compact epigenetic editor

Project description:Prion disease is caused by misfolding of the prion protein (PrP) into pathogenic self-propagating conformations, leading to rapid onset dementia and death. However, elimination of endogenous PrP can halt prion disease progression. Here, we describe CHARM, a compact, enzyme-free epigenetic editor capable of silencing transcription through programmable targeted DNA methylation. Using a histone H3 tail-Dnmt3l fusion, CHARM recruits and activates the endogenous DNA methyltransferases, thereby reducing transgene size and bystander effects. When delivered to the mouse brain by an adeno-associated viral (AAV) vector, PRNP-targeted CHARM ablates PrP expression across the brain. We temporally limit editor expression by implementing a kinetically-tuned self-silencing approach. CHARM represents a broadly applicable strategy to programmably prevent expression of pathogenic proteins, including those implicated in other neurodegenerative diseases.

2024-05-03 | GSE255987 | GEO

Genome editing in plants using the compact editor CasΦ

Project description:Genome editing in plants using the compact editor CasΦ

| PRJNA852208 | ENA

The compact high-fidelity EbCas12a enables all-in-one AAV delivery system

Project description:we characterized a novel compact Cas12a ortholog, EbCas12a, from the Erysipelotrichia bacterium with activities in mammalian cells. It is with the PAM sequence of 5’-TTTV-3’ (V=A, G, C) and the smallest size of ~3.47kb among reported Cas12a orthologs so far. Moreover, enhanced EbCas12a (enEbCas12a) was also developed to have comparable editing efficiency with higher specificity to AsCas12a and LbCas12a in mammalian cells. With the help of the compact enEbCas12a, all-in-one AAV delivery system with crRNA for Cas12a was developed for both in vitro and in vivo. Altogether, with the help of the novel smallest high fidelity enEbCas12a, this first case of the all-in-one AAV delivery for Cas12a could greatly boost future gene therapy and scientific research.

2023-07-10 | GSE236647 | GEO

Specific silencing of pathogenic mRNA by a novel compact RNA-targeting tool TaqTth-hpRNA

Project description:Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. However, the concern about the specificity of present RNA-knockdown strategies has limited their in vivo applications. Here a TaqTth-hpRNA system consisting of a small, chimeric protein (TaqTth) and hairpin-RNA probe (hpRNA) is provided. The TaqTth-hpRNA showed a high-specific knockdown against targeted mRNA with minimal flanking sequence-motif requirement and less cell viability damage, then was applied to mutant APPswe mRNA silencing without altering the wild-type APP mRNA in Alzheimer’s disease. Notably, the combination of the TaqTth and human apolipoprotein E 2 (APOE2) overexpression encoded in a single AAV vector is available due to the compact size of TaqTth, and showed stronger inhibition of pathologies in the mouse model. Altogether, we provided the basis for a small RNA-targeting tool with high selectivity, minimal flanking sequence-motif requirement, less cell viability damage and potentially being an alternative in therapeutic applications.

2024-06-30 | GSE236392 | GEO

The compact high-fidelity EbCas12a enables all-in-one AAV delivery system

Project description:The compact high-fidelity EbCas12a enables all-in-one AAV delivery system

| PRJNA991955 | ENA

Specific silencing of pathogenic mRNA by a novel compact RNA-targeting tool TaqTth-hpRNA [Amplicon sequencing]

2024-06-20 | GSE269593 | GEO

Specific silencing of pathogenic mRNA by a novel compact RNA-targeting tool TaqTth-hpRNA [RNA-seq]

2024-06-20 | GSE269592 | GEO

Transcriptional signature of prion-induced neurotoxicity in a Drosophila model of transmissible mammalian prion disease

Project description:Prion diseases are fatal transmissible neurodegenerative conditions of humans and animals that arise through neurotoxicity induced by PrP misfolding. The cellular and molecular mechanisms of prion-induced neurotoxicity remain undefined. Understanding these processes will underpin therapeutic and control strategies for human and animal prion diseases, respectively. Prion diseases are difficult to study in their natural hosts and require the use of tractable animal models. Here we used RNA-Seq-based transcriptome analysis of prion-exposed Drosophila to probe the mechanism of prion-induced neurotoxicity. Adult Drosophila transgenic for pan neuronal expression of ovine PrP targeted to the plasma membrane exhibit a neurotoxic phenotype evidenced by decreased locomotor activity after exposure to ovine prions at the larval stage. Pathway analysis and quantitative PCR of genes differentially expressed in prion-infected Drosophila revealed up-regulation of cell cycle activity and DNA damage response, followed by down-regulation of eIF2 and mTOR signalling. Mitochondrial dysfunction was identified as the principal toxicity pathway in prion-exposed PrP transgenic Drosophila. The transcriptomic changes we observed were specific to PrP targeted to the plasma membrane since these prion-induced gene expression changes were not evident in similarly-treated Drosophila transgenic for cytosolic pan neuronal PrP expression, or in non-transgenic control flies. Collectively, our data indicate that aberrant cell cycle activity, repression of protein synthesis and altered mitochondrial function are key events involved in prion-induced neurotoxicity, and correlate with those identified in mammalian hosts undergoing prion disease. These studies highlight the use of PrP transgenic Drosophila as a genetically well-defined tractable host to study mammalian prion biology.

2020-01-31 | GSE144028 | GEO

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

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

| PRJNA1104998 | ENA

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

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

| PRJNA1108200 | ENA