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Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells

ABSTRACT: Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells

PROVIDER: PRJNA950939 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24033833.fastq.gz	Fastqsanger.gz
	SRR24033834.fastq.gz	Fastqsanger.gz
	SRR24033835.fastq.gz	Fastqsanger.gz
	SRR24033836.fastq.gz	Fastqsanger.gz
	SRR24033837.fastq.gz	Fastqsanger.gz

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Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells

Project description:Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vector for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful AAV gene transfer. In contrast to anti-vector adaptive immunity, the initiation of the innate immunity towards rAAV is still poorly understood but is directly dependent on the interaction between the viral vector and innate immune cells. Here, we used a quantitative transcriptomic-based approach to determine the activation of inflammatory and anti-viral pathways after rAAV8-based infection of monocyte-derived Dendritic Cells (moDC) obtained from 12 healthy human donors. We have shown that rAAV8 particles are efficiently internalized, but that this uptake does not induce any detectable transcriptomic change in moDC cells in contrast to an adenoviral infection which upregulates anti-viral pathways. These findings suggest an immunological favorable profile for rAAV8 serotype with regards to in vitro activation of moDC cell model. Transcriptomic analysis of rAAV-infected innate immune cells is a powerful method to determine the ability of the viral vector to be seen by these sensor cells, which remains of great importance to better understand the immunogenicity of rAAV vectors and to design immune-stealth products.

2023-09-12 | GSE228649 | GEO

Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells.

Project description:Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vectors for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful AAV gene transfer. In contrast to antivector adaptive immunity, the initiation of the innate immunity towards rAAV is still poorly understood but is directly dependent on the interaction between the viral vector and innate immune cells. Here, we used a quantitative transcriptomic-based approach to determine the activation of inflammatory and anti-viral pathways after rAAV8-based infection of monocyte-derived dendritic cells (moDCs) obtained from 12 healthy human donors. We have shown that rAAV8 particles are efficiently internalized, but that this uptake does not induce any detectable transcriptomic change in moDCs in contrast to an adenoviral infection, which upregulates anti-viral pathways. These findings suggest an immunologically favorable profile for rAAV8 serotype with regard to in vitro activation of moDC model. Transcriptomic analysis of rAAV-infected innate immune cells is a powerful method to determine the ability of the viral vector to be seen by these sensor cells, which remains of great importance to better understand the immunogenicity of rAAV vectors and to design immune-stealth products.

| S-EPMC10341499 | biostudies-literature

Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells

Project description:rAAV8 does not activate human monocyte-derived Dendritic Cells

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Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells

Project description:rAAV8 does not activate human monocyte-derived Dendritic Cells

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Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells

Project description:No sensing of rAAV8 by human monocyte-derived dendritic cells

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RNA-seq of rd1 retinal microglia after treatment with AAV8-GFP vs. AAV8-GFP + AAV8-TGFB1

Project description:RNA-seq of rd1 retinal microglia after treatment with AAV8-GFP vs. AAV8-GFP + AAV8-TGFB1

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RNA-seq of rd1 retinal microglia after treatment with AAV8-GFP vs. AAV8-GFP + AAV8-TGFB1

Project description:Transcriptional profiling of microglia (seven biological replicates per experimental condition) or non-microglia (four biological replicates total). One thousand microglia (CD11b+ Ly6G/Ly6C-) or non-microglia cells (CD11b-) from P30 rd1 (FVB) retinas infected with either AAV8-GFP or AAV8-GFP + AAV8-TGFB1 were sorted into 10 µL of Buffer TCL (Qiagen) containing 1% beta-mercaptoethanol and immediately frozen on dry ice. Samples were subsequently sent to the Broad Institute Genomics Platform for cDNA library synthesis and sequencing using a modified Smart-Seq2 protocol with an expected coverage of ~6 million reads per sample. Prior to analysis, reads were subjected to quality control measures and mapped to the GRCm38.p6 reference genome. Reads assigned to each gene were then quantified using featureCounts and normalized and analyzed for differential expression using DESeq2.

2020-02-21 | GSE145601 | GEO

Transcriptome profile of thioacetamide treated mice injected with AAV8 TBG eGFP and AAV8 TBG miR34b/c

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Transcription profiling by array of liver from C57BL6 mice transfected with AAV8 vectors expressing either GFP or human macrophage inhibitory factor (MIF) or none (PBS).

Project description:MIF is a general mediator of inflammatory responses and is associated with several inflammatory diseases including atherosclerosis. Therefore MIF is currently investigated as a therapeutic target for atherosclerosis. Generation of AAV8 vectors expressing human MIF was initiated to overexpress human MIF in AAV8 target tissues (liver, heart, muscles) of C57/Bl6 to study biological function of MIF in vivo and to provide an animal model for testing of MIF antibodies. Aim of the gene expression profiling experiment: Livers of AAV8-CMV-MIF treated animals in order to identify established and potential novel target genes of MIF induced signalling

2013-03-07 | E-MTAB-1019 | biostudies-arrayexpress

Transcriptome profile of thioacetamide treated mice injected with AAV8 TBG eGFP and AAV8 TBG miR34b/c

Project description:Transcriptome profile of thioacetamide treated mice injected with AAV8 TBG eGFP and AAV8 TBG miR34b/c

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