Cynomolgus macaques treated with Divalent-siRNA (Di-siRNA) targeting Huntingtin gene
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA534060 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Examine potential off-target effects of HTT targeting siRNA in cynomologus macaque brains.
2019-08-26 | GSE130132 | GEO
Project description:The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed evaluation of safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a system biology approach to compare hematological, biochemical, transcriptomic, innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination. Immune response progression in cynomolgus macaques followed a similar course as in adult humans, but with slightly earlier onset. Yellow fever virus neutralizing antibody responses occurred earlier in cynomolgus macaques (by Day 7 [D7]), but titers >10 were reached in both species by D14 post-vaccination and were not significantly different by D28 (PRNT50 titers 3.6 Log vs 3.5 Log in cynomolgus macaques and human participants, respectively; p = 0.821). Changes in neutrophils, NK cells, monocytes, T and B cell frequency were higher in cynomolgus macaques and persisted for four weeks versus less than two weeks in humans. Low levels of systemic inflammatory cytokines (IL-1Ra, IL-8, MIP-1α, IP-10, MCP-1 or VEGF) were detected in either or both species, but with no or only slight changes versus baseline. Similar changes in gene expression profiles were elicited in both species. These included enriched and up-regulated type I IFN-associated viral sensing, antiviral innate response, and dendritic cell activation pathways D3–D7 post-vaccination in both species. Hematological and blood biochemical parameters remained relatively unchanged versus baseline in both species. Low level YF-17D viremia (RNAemia) was transiently detected in some cynomolgus macaques (28% [5/18]) but generally absent in humans (except one participant [5%; 1/20]). Importance: Cynomolgus macaques were confirmed as a valid surrogate model for replicating YF-17D vaccine-induced responses in humans, and suggest a key role for type I IFN.
2024-03-29 | GSE253538 | GEO
Project description:We performed gene expression profiling of total RNA from brain samples derived from BSE-infected versus non-infected cynomolgus macaques (Macaca fascicularis).
2014-06-10 | GSE52436 | GEO
Project description:In this study, we established the COVID-19 infection model in cynomolgus macaques (CMs), the differentially expressed proteins was analyzed in lung tissue collected from 3 untreated (NC1-3) and 4 CMs inoculated with SARS-CoV-2 for 7 days (nCoV1-4). The results showed the differentially expressed genes (DEGs) before and after exposure. The median CV values was analyzed to confirm the proteomics data with good degree of consistency and reproducibility (median<0.25). The histogram of GO terms enriched in biological process, cellular component and molecular function.
2022-07-06 | PXD034589 | Pride
Project description:Background: Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results: Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions: We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration. Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. In a second approach, ERV-K-(HML-2) RNA and protein expression was analysed in extracts from the same cynomolgus macaques.
2011-06-10 | E-GEOD-29818 | biostudies-arrayexpress
Project description:Microarray analysis of PBMC from cynomolgus macaques collected longitudinally over the course of infection with Lassa-Josiah, Lassa-Z132, Lassa-SorombaR, or Lujo viruses (n=3 animals/infection condition).
2014-08-29 | GSE49838 | GEO
Project description:We performed gene expression profiling of total RNA from brain samples derived from BSE-infected versus non-infected cynomolgus macaques (Macaca fascicularis). Total RNA from brain samples derived from 7 BSE-infected (6 intracerebrally, 1 orally infected) versus 5 non-infected controls were compared using GeneChip Rhesus macaque Genome Array.
2014-06-10 | E-GEOD-52436 | biostudies-arrayexpress
Project description:Recombinant insect baculoviral vectors efficiently transduce several types of cells in the brain and can possibly be used for gene therapy for brain disorders. To verify the suitability of using these viral vectors to develop gene therapy strategies in the brain, we evaluated immune reactions upon acute administration of baculoviral vectors into the brain of the cynomolgus macaque using microarray global gene expression profiling. Adult male cynomolgus macaques (Macaca fascicularis) were administered with baculovirus BV-HSVtk purified by membrane chromatography + high-speed centrifugation (MC+HS) into the brain.
2015-11-21 | E-GEOD-75264 | biostudies-arrayexpress
Project description:Microarray analysis of PBMC from cynomolgus macaques collected longitudinally over the course of infection with Lassa-Josiah, Lassa-Z132, Lassa-SorombaR, or Lujo viruses (n=3 animals/infection condition). 3 macaques from each group were infected intramuscularly with 10^4 PFU of Lassa-Josiah, Lassa-Z132, Lassa-SorombaR, or Lujo viruses. PBMC were collected at days 1, 4, 7, 10, 13, and 29 (for surviving animals). We performed microarray analysis on PBMC samples using Agilent rhesus macaque arrays on all samples, as well as on PBMC from 3 uninfected animals for use as a control.
2014-08-29 | E-GEOD-49838 | biostudies-arrayexpress
Project description:Succesful xenotransplantation of porcine kidneys into humans requires durable expression of certain human transgenes. In order to ensure robust expression through the life of the transplanted kidney, RNA-seq was performed on gene-edited kidneys prior to and during transplantation into cynomolgus macaques. Analysis of this longitudinal transcriptomics data shows robust and stable transgene expression through the lifespan of numerous xenotransplanted organs.
2023-04-21 | GSE210556 | GEO