Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuroprotective effect of miR-204 OE in mouse models of Inherited Retinal Disease (IRD)

ABSTRACT: Transcriptome profile of retinas from wild-type (c57BL/6) and RHO-P347S mice following AAV-mediated subretinal delivery of pre-miR-204 to study the molecular changes underlying the neuroprotective effect of miR-204 OE in mouse models of Inherited Retinal Disease (IRD) To determine the molecular changes associated with AAV-mediated delivery of miR-204 in the subretinal space of wild-type and IRD mouse models, we performed RNASeq analysis of retinas from c57BL/6 and RHO-P347S mice injected with the AAV2/8.CMV.miR204 and AAV2/8.CMV.miR204MUT vector in a paired manner.

ORGANISM(S): Mus musculus

PROVIDER: GSE121785 | GEO | 2019/12/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Retinitis pigmentosa (RP) mouse cone transcriptom change with Txnip treatment

Project description:Purpose: To identifiy mRNA changes in retinitis pigmentosa (RP) cone photoreceptors with Txnip overexpression treatment, which improved RP cone survival and visual acuity. Methods: two RP mouse strains, rd1 and Rho-/-, were injected with AAV-Txnip or AAV-H2BGFP control subretinally at P0. Retinas were dissected out at P21 for rd1 and P90 for Rho-/-. 1,000 H2BGFP labeled cones per retina sample were FACS sorted out, and subject for RNA-sequencing. Results: >1,400 genes in P21 rd1 and >700 genes in Rho-/- were found differentially expressed with Txnip treatment. Conclusions: 25 genes are in common between P21 rd1 and P90 Rho-/- with Txnip treatment. On this list, notably, three mitochondrial Electron Transport Chain (ETC) genes were up-regulated.

2021-01-20 | GSE161622 | GEO

A novel capsid-XL32-derived adeno-associated virus serotype prompts retinal tropism and ameliorates choroidal neovascularization

Project description:Gene therapy has been adapted, from the laboratory to the clinic, to treat retinopathies. In contrast to subretinal route, intravitreal delivery of AAV vectors displays the advantage of bypassing surgical injuries, but the viral particles are more prone to be nullified by the host neutralizing factors. To minimize such suppression of therapeutic effect, especially in terms of AAV2 and its derivatives, we introduced three serine-to-glycine mutations, based on the phosphorylation sites identified by mass spectrum analysis, to the XL32 capsid to generate a novel serotype named AAVYC5. Via intravitreal administration, AAVYC5 was transduced more effectively into multiple retinal layers compared with AAV2 and XL32. AAVYC5 also enabled successful delivery of anti-angiogenic molecules to rescue laser-induced choroidal neovascularization and astrogliosis in mice and non-human primates. Furthermore, we detected fewer neutralizing antibodies and binding IgG in human sera against AAVYC5 than those specific for AAV2 and XL32. Our results thus implicate this capsid-optimized AAVYC5 as a promising vector suitable for a wide population, particularly those with undesirable AAV2 seroreactivity.

2023-12-04 | PXD047487 | iProX

Instability of WT AAV2 genome and AAV promoter activities in the Baculovirus/Sf9 cells system

Project description:The human Adeno-Associated Virus serotype 2 (WT AAV2) is a common non-pathological virus and its recombinant form (rAAV) is widely used as gene therapy vector. However, it has been shown that WT AAV2 and recombinant AAV display significantly different characteristics, especially regarding infection rate, with a near perfect infectivity and better encapsidation rate of WT AAV2. Even though rAAVs are routinely produced in the Baculovirus/Sf9 cell system, WT AAV2 has never been produced in this context. To understand the infectivity and encapsidation rate differences between WT AAV2 and rAAV, we tried to produce WT AAV2 in baculovirus/Sf9 cells system hypothesizing that the WT AAV2 may be considered as a normal recombinant AAV transgene. Through our attempts to produce WT AAV2 in Baculovirus/Sf9, we found that WT AAV2 p5 promoter, which controls the expression of large Rep proteins in mammalian cells, was active in this system. p5 promoter activity in the baculovirus/Sf9 cell system led to the expression of Rep78 that finally excises WT AAV2 genome from the baculovirus genome during the earliest phase of baculovirus stock production. The p5 promoter expression kinetics and the specific strand RNA-Seq analysis of the WT AAV2, rAAV Rep2/Cap2 cassettes in the baculovirus context was performed. We demonstrate that the WT AAV2 native promoters, p5, p19 and p40 are all active and lead to the expression of different proteins and peptides. In addition, this study demonstrates that the baculovirus brings at least some of the helper functions needed in the AAV replication/life cycle.

2018-06-21 | GSE96855 | GEO

Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

Project description:The deregulation of microRNAs (miRNAs) has been demonstrated to be involved in tumor angiogenesis and offers opportunities for a new therapeutic approach. However, effective miRNA delivery systems are needed for such approaches to be successful. In this study, miRNA profiling of patient data sets, along with in vitro and in vivo experiments, revealed that miR-204-5p could promote angiogenesis in ovarian tumors through THBS1. To identify potential molecular mechanisms by which miR-204-5p exerts its pro-angiogenic effects, we performed a gene expression microarray of HeyA8-MDR cells following treatment with miR-204-5p-inh.

2019-02-28 | GSE120585 | GEO

The Adeno-Associated Virus 2 (AAV2) genome and Rep 68/78 proteins interact with cellular sites of DNA damage.

Project description:We have previously developed a modified iteration of a viral chromosome conformation capture (V3C-seq) assay to show that the autonomous parvovirus Minute Virus of Mice (MVM) localizes spatially with cellular sites of DNA damage to establish viral replication centers. Similar V3C-seq assays to map AAV genome localization show that both replicating and non-replicating AAV2 genomes in the absence of helper virus colocalize with cellular sites of DNA damage. The AAV non-structural protein Rep 68/78, when ectopically expressed in the absence of viral infection or during AAV2 infection in the absence of helper proteins also localizes to cellular sites of DNA damage. Strikingly however, recombinant AAV gene therapy vector genomes derived from AAV do not colocalize with AAV and Rep at cellular DDR sites.

2021-10-20 | GSE178316 | GEO

Neuroprotective effect of miR-204 OE in mouse models of Inherited Retinal Disease (IRD)

Project description:Neuroprotective effect of miR-204 OE in mouse models of Inherited Retinal Disease (IRD)

| PRJNA498424 | ENA

Small and large RNA sequencing of mouse livers receiving small hairpin RNAs

Project description:Adeno-associated viral (AAV) small hairpin (shRNA) expression vectors are a promising therapeutic but can induce severe liver toxicity when delivered at high albeit undefined doses. Using various AAV-shRNA vectors under the high-expressing U6 and low-expressing H1 promoters, we found that dose-limiting toxicity was strongly correlated with an shRNA concentration of >12% of total microRNA levels. Toxicity was associated with a specific reduction in the first synthesized 22nt isoform of miR-122-5p, resulting in the specific de-repression of miR-122 target mRNAs. A causative link between miR-122 reduction and toxicity was established when an AAV-sh-miR-122 vector producing >20% of the total liver miRNAs prevented liver toxicity. Consistent with these results, miR-122 knockout mice, which in part adapt to an absence of miR-122 reduction, also show no toxicity with high dose AAV-shRNA delivery. RNA sequencing of 12 liver samples, 2 receiving H1-shRNAs, 7 with U6-shRNAs and 3 controls; small RNA sequencing of 95 samples including 18 with CMV-driven miR-122 expression in HEK293 cells, 13 in miR-122 knockout mice, 9 samples in mice heterozygous for miR-122, 5 samples with Cre-mediate excision of miR-122, 19 samples immunoprecipitated with Ago2 and 31 additional liver samples (3 control, 11 receiving H1-shRNAs and 17 receiving U6-shRNAs). Small RNA libraries were barcoded (first 4 nucleotides) at the 5' end and ligated to linker-1 (5'-CTGTAGGCACCATCAAT) at the 3' end.

2016-03-09 | E-GEOD-69186 | biostudies-arrayexpress

Expression values from wild-type retinas and retinas with a mutant Rhodopsin transgene (Tg(RHO P347S)) with and without Endothelin-2 (EDN2)

Project description:Expression of the Endothelin-2 (Edn2) mRNA is greatly increased in the photoreceptors (PRs) of mouse models of inherited PR degeneration. To identify retinasl gene whose expression is directly or indirectly regulated by EDN2 in the presence of the Tg(RHO P347S) mutant allele, we defined mRNAs that were differentially expressed in Edn2+/+, Edn2-/-, Tg(RHO P347S) Edn2+/+, and Tg(RHO P347S) Edn2-/- retinas. RNA was extracted from Edn2+/+, Edn2-/-, Tg(RHO P347S) Edn2+/+, and Tg(RHO P347S) Edn2-/- retinas at postnatal day 21 (PN21) and hybridized to Affymetrix arrays

2012-07-15 | E-GEOD-38797 | biostudies-arrayexpress

Small and large RNA sequencing of mouse livers receiving small hairpin RNAs

2016-03-09 | GSE69186 | GEO

Genotoxicity after adeno-associated virus (AAV) gene therapy is dependent upon dose, treatment age and enhancer-promoter selection

Project description:AAV gene therapy has recently been approved for clinical use and shown to be efficacious and safe in a growing number of clinical trials. However, the safety of AAV as a gene therapy has been challenged by a few studies that documented hepatocellular carcinoma (HCC) after AAV gene delivery in mice. The association between AAV and HCC has been difficult to reconcile and is the subject of intense debate because numerous AAV studies have not reported toxicity. Here, we report a comprehensive study of HCC in a large number of mice following therapeutic AAV gene delivery. Using a sensitive high-throughput integration site-capture technique and global expressional analysis, we found that AAV integration into the Rian locus and the over-expression of a proximal gene, Rtl1, were associated with HCC. In addition, we identify a number of genes with differential expression that maybe useful in the study, diagnosis and treatment of HCC. We demonstrate that AAV vector dose, enhancer-promoter selection, and the timing of gene delivery are the defining factors in AAV-mediated insertional mutagenesis. Our results help explain the AAV-mediated genotoxicity previously observed and have important implications for the design of both safer AAV vectors and gene therapy studies. To investigate the possibility that insertional mutagenesis by AAV contributed to the development of HCC, we collected normal and tumor tissues from adult mouse livers that received AAV injection at a neonatal stage.

2015-01-01 | E-GEOD-57597 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data