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ABSTRACT: ABE for Liver

PROVIDER: PRJNA725910 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14368600_1.fastq.gz	Fastqsanger.gz
	SRR14368600_2.fastq.gz	Fastqsanger.gz
	SRR14368700_1.fastq.gz	Fastqsanger.gz
	SRR14368700_2.fastq.gz	Fastqsanger.gz
	SRR14368601_1.fastq.gz	Fastqsanger.gz

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Project description:ABE

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Abe_et_al_Nature_Communications_2022_mass_spectrometry_rawdata

Project description:This is supplemental raw data for Abe et al., 2022. Proteome analysis and phospho-proteome analysis using mouse liver prepared at 6 circadian time points (CT2, 6, 10, 14, 18, 22). In the delta-RRE mutant, two RRE sequences are removed from 5'UTR of mouse Bmal1 gene.

2022-07-20 | PXD035414 | Pride

Adenine base editors induce off-target structure variations in mouse embryos and primary human T cells

Project description:Background The safety of CRISPR-based gene editing methods is of the utmost priority in clinical applications. Previous studies have reported that Cas9 cleavage induced frequent aneuploidy in primary human T cells, but whether cleavage-mediated editing of base editors would generate off-target structure variations remains unknown. Here, we investigated the potential off-target structural variations associated with CRISPR/Cas9, ABE and CBE editing in mouse embryos and primary human T cells by whole-genome sequencing and single-cell RNA-seq analyses. Results The results showed that both Cas9 and ABE generated off-target structural variations (SVs) in mouse embryos, while CBE induced rare SVs. In addition, off-target large deletions were detected in 32.74% of primary human T cells transfected with Cas9 and 9.17% of cells transfected with ABE. Moreover, Cas9-induced aneuploid cells activated the P53 and apoptosis pathways, whereas ABE-associated aneuploid cells significantly upregulated cell cycle-related genes and arrested in G0 phase. A percentage of 16.59% and 4.29% aneuploid cells were still observable at 3 weeks post transfection of Cas9 or ABE. These off-target phenomena in ABE were universal as observed in other cell types such as B cells and Huh7. Furthermore, the off-target SVs were significantly reduced in cells treated with high-fidelity ABE (ABE-V106W). Conclusions This study raises urgent need for minimizing the off-target SVs of CRISPR/Cas9 and ABE.

2024-11-01 | GSE280767 | GEO

Estrogen-like activity and dual roles in cell signaling of an Agaricus blazei Murrill mycelia-dikaryon extract

Project description:Comparing the expression profiles of the genes in response to 17b-estradiol (E2) and Agaricus blazei extract (ABE) Two-condition experiment, E2- or ABE-treated vs. control cells. 2 to 3 biological replicates, independently grown and harvested. Two to three replicates per array.

2014-01-01 | E-GEOD-30193 | biostudies-arrayexpress

Project description:ABE-mismatch

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Homo sapiens strain:HEK293T

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In vivo adenine base editing of PCSK9 in mice and macaques reduces LDL-cholesterol levels [RNA-seq]

Project description:The majority of known pathogenic point mutations in the human genome are C•G to T•A substitutions. Adenine base editors (ABEs), comprised of nuclease-impaired Cas9 fused to adenine deaminases, enable direct repair of these mutations, making them promising tools for precision in vivo genome editing therapies. However, prior to application in patients, thorough safety and efficacy studies in relevant model organisms are needed. Here, we apply adenine base editing in vivo in the liver of mice and cynomolgus macaques to install a splice site mutation in PCSK9 and reduce blood low-density lipoprotein (LDL) levels, a well-known risk factor for cardiovascular disease. Intravenous delivery of ABE-encoding mRNA and a locus-specific single guide (sg)RNA utilizing lipid nanoparticle (LNP) technology induce up to 67% editing in the liver of mice and up to 34% editing in the liver of macaques, leading to a reduction of plasma PCSK9 and LDL levels. We observed rapid clearance of ABE mRNA after LNP-mediated delivery, and neither sgRNA-dependent nor sgRNA-independent off-target mutations are detected in genomic DNA. Together, our findings support safety and feasibility of adenine base editing to treat patients with monogenetic liver diseases.

2021-04-13 | GSE168363 | GEO

In vivo adenine base editing of PCSK9 in mice and macaques reduces LDL-cholesterol levels [amplicon-seq]

2021-04-13 | GSE168364 | GEO

Enhanced solvent titer in the fermentation of Clostridium beijerinckii through application of metabolic controls

Project description:Clostridium beijerinckii is an anaerobic strain and well known for acetone-ethanol-butanol (ABE) fermentation using carbohydrates derived from cellulose or starch. During ABE fermentation, various byproducts are formed, mainly including acids (acetate, butyrate and lactate) and gas (hydrogen and carbon dioxide). recently, we found that Clostridium beijerinckii is able to produce a new product that had never been reported before and tightly regulated by pH and nitrogen source.

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Project description:To alleviate the ABE-mediated cytosine editing activity, we engineered the commonly-used version of adenosine deaminase, TadA7.10. We found that the D108Q mutation also reduces cytosine deamination activity in two recently-developed versions of ABE, ABE8e and ABE8s, and has a synergistic effect with V106W, a key mutation that reduces off-target RNA editing.

2021-01-21 | GSE165164 | GEO

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