A Biodistribution Study of OTV vs. ASO by Intravenous or Intrathecal Administration in Cynomolgus Monkeys
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PROVIDER: PRJNA858409 | ENA |
REPOSITORIES: ENA
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Project description:The objective of this study is to evaluate ASO biodistribution and pharmacodynamic response following intravenous delivery of conjugated OTV, which utilizes transferrin-receptor binding to deliver ASO, vs. intrathecal delivery of naked ASO in cynomolgus monkeys, the current gold standard for ASO delivery. Three groups were included for comparison: 1) Negative control cohort = Four biweekly intravenous doses of saline (n=3); 2) IT cohort = Single intrathecal dose of 4mg MALAT1 ASO (n=3); 3) OTV multi dose cohort = Four biweekly intravenous doses of 30mpk OTV:MALAT1 (n=3). Tissues were collected two weeks after the final dose to allow sufficient time for target knockdown. Brain, spinal cord, and peripheral tissues were dissected and frozen for molecular analysis. Compared to an intrathecal injection of ASO, systemic administration of OTV resulted in significantly more homogenous biodistribution of ASO in the central nervous system as measured by a probe-based hybridization assay as well as staining with an anti-ASO antibody. One potential consequence of heterogeneous ASO distribution is heterogeneous target knockdown throughout the CNS. We observed more consistent target knockdown throughout the cortex, subcortical areas, and spinal cord of monkeys dosed peripherally with OTV. By contrast, monkeys dosed intrathecally with naked ASO showed much more knockdown in the spinal cord compared to the brian, consistent with ASO distribution.
2024-02-12 | GSE208114 | GEO
Project description:Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls.
2023-06-23 | PXD036423 | Pride
Project description:To identify plasma proteomics changes in primates aging and aging intervention, we performed DIA sequencing on blood plasma from the cynomolgus monkeys.
2024-03-05 | PXD050387 |
Project description:EXPERIMENT: The animal experiments were performed at Shin Nippon Biomedical Laboratories (SNBL), Ltd. (Kagoshima, Japan) in compliance with the Guideline for Animal Experimentation (1987), and in accordance with the Law Concerning the Protection and Control of Animals (1973) and the Standards Relating to the Care and Management of Experimental Animals (1980). This study was approved by the Institutional Animal Care and Use Committee of SNBL and performed in accordance with the ethics criteria contained in the bylaws of the SNBL committee. Each female monkey was paired with a male of proven fertility for one day between day 11 and day 15 of the menstrual cycle. Pregnant females, aged 5-8 years and weighing 2.84-3.76 kg on day 22 of gestation, were allocated randomly to two groups, each with three monkeys, and housed individually. The monkeys were orally dosed with (±)-thalidomide (Lot no. SDH7273/SDJ3347, Wako Pure Chemical Industries, Ltd., Osaka, Japan) at 0 or 20 mg/kg by oral intubation on day 26 of gestation, which was during the critical period for thalidomide-induced teratogenesis [Delahunt and Lassen, 1964; Hendrickx, 1973]. Dosage was adjusted to the body weight on day 22 of gestation and the drug was packed in a gelatin capsule. Control monkeys received the capsule only. ANIMAL MODEL: Macaca fascicularis INTERVAL: NON. PLATFORM: Proprietary Affymetrix NHP GeneChip® Array for Cynomolgus genome derived from Biogen Idec Keywords = Developmental Keywords = Monkeys Keywords = Thalidomide TFetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomidechannel oligonucleotide (Affymetrix) platform.
2010-06-20 | E-GEOD-15542 | biostudies-arrayexpress
Project description:Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. To evaluate organ transcriptomes and gene expression variability in Cynomolgus monkeys, we used Customized NimbleGen Microarrays (Design ID: 120419_Cynomolgus_v5_TH_exp_HX12) for genome-wide gene expression profiling on 5 different tissues (heart, kidney, liver, lung, spleen) from 21 Cynomolgus monkeys. Cynomolgus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 females and 2 males), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore, genome-wide copy number variation was analyzed in tissue samples from the same animals using a custom NimbleGen 4.2 million probes comparative genomic hybridization (CGH) array to associate CNV genotypes with expression changes of proximal genes.
2016-02-24 | GSE76560 | GEO
Project description:Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. Cynomolgus monkeys are outbred species and exhibit substantial levels of genetic variation which can affect the outcome and interpretation of biomedical studies. Copy number variations (CNVs) are a significant source of genetic diversity and a comprehensive understanding of the genomic impact of CNVs on phenotypic traits is limited. A custom 4.2 million probes comparative genomic hybridization (CGH) array (Design-ID: 120405_Cynomolgus5_CGH_UX1) has been designed on the basis of the Cynomolgus monkey genome (Ebeling et al. (2011) Genome Research; PMID: 21862625) to assess genome-wide copy number variation among Cynomolgus monkeys. Using Cynomolgus monkey specific NimbleGen CGH Microarrays we profiled the genomes of 21 Cynomolgus monkeys. Germline DNA from 21 Cynomolgus monkeys with different origin was tested against a Cynomolgus monkey reference. Cynomolus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 males and 2 females), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore genome-wide expression profiles were analyzed in 5 vitally important tissue samples (heart, kidney, liver, lung, spleen) from the same animals using a custom Cynomolgus monkey specific NimbleGen gene expression microarray (design ID: 120419_Cynomolgus_v5_TH_exp_HX12) to associate CNV genotypes with expression changes of proximal genes using a cis expression quantitative trait loci (cis-eQTL) mapping approach. Expression data have been deposited at the NCBI Gene Expression Omnibus (GEO) under accession numbers GSE76560. The array CGH results analyzed in this study are further described in Gschwind A.R. et al. (2016) "Diversity and regulatory impact of copy number variation in the primate Macaca fascicularis". under submission
2016-02-24 | GSE76707 | GEO
Project description:Lassa fever outbreaks hit West African countries every year and there is still no licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine that induces protective immunity in cynomolgus monkeys one month or more than a year before Lassa virus infection and that is able to protect against divergent viral strains. Given the limited dissemination area of Lassa virus during outbreaks and the high risk of nosocomial transmission, a vaccine that induces rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. We tested whether the time to protection could be reduced after immunization by challenging MeV pre-immune cynomolgus monkeys 16 or 8 days after a single shot of MeV-NP. None of the immunized monkeys developed disease and they rapidly controlled viral replication. Animals immunized eight days before the challenge were the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated an hour after the challenge. These animals did not develop any protective immune responses and presented the same lethal disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine.
2023-02-21 | GSE225258 | GEO
Project description:OBJECTIVE: The regional heterogeneity of vascular components and transcriptomes is an important determinant of aortic biology. This notion has been explored in multiple mouse studies. In the present study, we examined the regional heterogeneity of aortas in non-human primates. APPROACH AND RESULTS: Aortic samples were harvested from the ascending, descending, suprarenal, and infrarenal regions of young control monkeys and adult monkeys provided with high fructose for 3 years. The regional heterogeneity of aortic structure and transcriptomes was examined by histological and bulk RNA sequencing analyses. Immunostaining of CD31 and αSMA revealed that endothelial and smooth muscle cells were distributed homogeneously across the aortic regions. In contrast, elastic fibers were less abundant and dispersed in the infrarenal aorta compared to other regions and associated with collagen deposition. Bulk RNA sequencing identified a distinct transcriptome related to the Notch signaling pathway in the infrarenal aorta with significantly increased NOTCH3 mRNA compared to other regions. Immunostaining revealed that NOTCH3 protein was increased in the media of the infrarenal aorta. The abundance of medial NOTCH3 was positively correlated with the dispersion of elastic fibers. Adult cynomolgus monkeys provided with high fructose displayed vascular wall remodeling, such as smooth muscle cell loss and elastic fiber disruption, predominantly in the infrarenal region. The correlation between NOTCH3 and elastic fiber dispersion was enhanced in these monkeys. CONCLUSION: Aortas of young cynomolgus monkeys display regional heterogeneity of their transcriptome and the structure of elastin and collagens. Elastic fibers in the infrarenal aorta are dispersed along with upregulation of medial NOTCH3.
2023-03-22 | GSE227434 | GEO
Project description:RNA sequencing of lung tissue of cynomolgus monkeys
| PRJNA630693 | ENA
Project description:EXPERIMENT: The animal experiments were performed at Shin Nippon Biomedical Laboratories (SNBL), Ltd. (Kagoshima, Japan) in compliance with the Guideline for Animal Experimentation (1987), and in accordance with the Law Concerning the Protection and Control of Animals (1973) and the Standards Relating to the Care and Management of Experimental Animals (1980). This study was approved by the Institutional Animal Care and Use Committee of SNBL and performed in accordance with the ethics criteria contained in the bylaws of the SNBL committee. Each female monkey was paired with a male of proven fertility for one day between day 11 and day 15 of the menstrual cycle. Pregnant females, aged 5-8 years and weighing 2.84-3.76 kg on day 22 of gestation, were allocated randomly to two groups, each with three monkeys, and housed individually. The monkeys were orally dosed with (±)-thalidomide (Lot no. SDH7273/SDJ3347, Wako Pure Chemical Industries, Ltd., Osaka, Japan) at 0 or 20 mg/kg by oral intubation on day 26 of gestation, which was during the critical period for thalidomide-induced teratogenesis [Delahunt and Lassen, 1964; Hendrickx, 1973]. Dosage was adjusted to the body weight on day 22 of gestation and the drug was packed in a gelatin capsule. Control monkeys received the capsule only. ANIMAL MODEL: Macaca fascicularis INTERVAL: NON. PLATFORM: Proprietary Affymetrix NHP GeneChip® Array for Cynomolgus genome derived from Biogen Idec Keywords = Developmental Keywords = Monkeys Keywords = Thalidomide
2009-11-01 | GSE15542 | GEO