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Single-nuclei RNA sequencing analysis from a WT mouse brain cortex after Intrathecal(IT) injection of AAV9/JeT-hSLC6A1 vector

ABSTRACT: Single-nuclei RNA sequencing analysis from a WT mouse brain cortex after Intrathecal(IT) injection of AAV9/JeT-hSLC6A1 vector

PROVIDER: PRJNA1168537 | ENA |

REPOSITORIES: ENA

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Single-nuclei RNA sequencing analysis from a WT mouse brain cortex after Intrathecal(IT) injection of AAV9/JeT-hSLC6A1 vector

Project description:Single-nuclei RNA sequencing analysis conducted at 6 months old from a WT mouse brain cortex, following Intrathecal(IT) injection of AAV9/JeT-hSLC6A1 vector at PND10.

2025-01-08 | GSE278732 | GEO

AAV9 vector batch sequencing

Project description:Recombinant AAV9 with a SEAP reporter transgene sequenced by nanopore and SMRT

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Single-cell RNA sequencing of mouse forebrain cells 5 weeks after injections of a control AAV9 or a VEGF-C/D trap AAV9

Project description:In this work we have induced meningeal lymphatic ablation by decreasing the circulating levels of VEGF-C and -D (VEGF-C/D trap), via injection of an AAV9 expressing domains 1 to 3 of murine VEGFR3 coupled to an Ig domain (VEGF-C/D trap). Control mice were injected with an AAV9 expressing domains 4 to 7 of murine VEGFR3 coupled to an Ig domain (controls). 5 weeks upon the initial injections, animals were perfused, and the forebrain tissue was collected and processed for single-cell RNA sequencing (10x Genomics).

2024-07-31 | GSE230709 | GEO

ASS lime injection - injection site

Project description:ASS lime injection - injection site

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Adeno-associated virus-mediated trastuzumab delivery to the central nervous system for human epidermal growth factor receptor 2+ brain metastasis

Project description:Trastuzumab improves overall survival for HER2+ breast cancer, but its short half-life in the cerebral spinal fluid (~2-4 days) and delivery limitations restrict the ability to target HER2+ central nervous system (CNS) disease.We developed an adeno-associated virus (AAV) vector expressing a codon-optimized, ubiquitin C (UbC)-promoter-driven trastuzumab sequence (AAV9.UbC.trastuzumab) for intrathecal administration. Transgene expression was evaluated in adult Rag1 knockout mice and rhesus nonhuman primates (NHPs) after a single intracerebroventricular (ICV) or intra-cisterna magna (ICM) AAV9.UbC.trastuzumab injection, respectively, using real-time PCR, ELISA, Western blot, in situ hybridization, single-nucleus RNA sequencing, and liquid chromatography-mass spectrometry; antitumor efficacy was evaluated in brain xenografts using HER2+ breast cancer cell lines (BT-474, MDA-MB-453).Transgene expression was detected in brain homogenates of Rag1 knockout mice following a single ICV injection of AAV9.UbC.trastuzumab (1×1011 vector genome copies [GC]/mouse) and tumor progression was inhibited in xenograft models of breast-to-brain metastasis. In NHPs, ICM delivery of AAV9.UbC.trastuzumab (3×1013 GC/animal) was well tolerated (36–37 days in-life) and resulted in transgene expression in CNS tissues and cerebrospinal fluid at levels sufficient to induce complete tumor remission in MDA-MB-453 brain xenografts. With AAV9’s proven clinical safety record, this gene therapy may represent a viable approach for targeting HER2+ CNS malignancies.

2024-02-05 | GSE255027 | GEO

Expression data for P. aeruginosa ATCC 33988 and P. aeruginosa PAO1 in Jet-A fuel

Project description:We investigated fuel specific transcriptomic differences between these strains in order to ascertain the underlying mechanisms utilized by the adapted strain P. aeruginosa ATCC 33988 to jet fuel to Jet-fuel During growth in fuel, the genes related to alkane degradation, heat-shock response, membrane proteins, efflux pumps and several novel genes were upregulated in ATCC 33988

2017-01-10 | GSE93305 | GEO

Systemic Delivery of an AAV9 Exon Skipping Vector Significantly Improves or Prevents Features of Duchenne Muscular Dystrophy in the Dup2 Mouse Model

Project description:Purpose: Duchenne muscular dystrophy (DMD) is typically caused by mutations that disrupt the DMD reading frame, but nonsense mutations in the 5’ part of the gene lead to the utilization of an internal ribosomal entry site (IRES) in exon 5, resulting in expression of a highly functional N-truncated dystrophin. We have developed an AAV9 vector expressing U7 small nuclear RNAs targeting DMD exon 2 and tested it in a mouse model containing a duplication of exon 2, in which skipping of both exon 2 copies results in IRES-induced expression, and skipping of only one exon 2 leads to wild-type dystrophin expression. Methods: One-time intravascular injection of an AAV9 vector expressing U7 small nuclear RNAs targeting Dmd exon 2 at either P0-P1 or at 2 months of age results in efficient exon skipping and dystrophin expression, and significant protection from functional and pathologic deficits. Results: In mice treated neonatally, dystrophin immunofluorescence reached 49-85% of normal signal intensity and 76-99% dystrophin-positive fibers, with near-complete correction of dystrophic pathology, and these beneficial effects showed no significant signs of declining for at least 6 months. RNA sequencing (RNA-Seq) and Ribosome Profiling (RPF-Seq) indicated that treatment restored a ‘non-dystrophic’ gene expression profile by reversing the direction and magnitude of differentially expressed genes previously identified in dystrophic skeletal muscle from DMD patients. The dystrophin transcript showed clearly increased RPF reads in the treated sample, indicating that the treatment specifically increased dystrophin translation. Conclusions: The results demonstrate the robustness, durability, and safety of exon 2 skipping following delivery of scAAV9.U7snRNA.ACCA, supporting its clinical use.

2022-01-29 | GSE195480 | GEO

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ASS lime injection - injection site metagenomic assembly

Project description:EMG produced TPA metagenomics assembly of the ASS lime injection - injection site (ASS lime injection - injection site) data set

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Hydrocarbons (Jet Fuel JP-8) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

Project description:Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures. Methylated sperm DNA was isolated from rats ancestrally exposed to jet fuel (Jip). Three independent samples from the treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. Treated samples were paired with control samples and hybridized together on arrays (Jip1/Cip1, Jip2/Cip2, and Jip3/Cip3), resulting in three arrays for the treatment.

2014-07-22 | E-GEOD-59553 | biostudies-arrayexpress

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