Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of liver from Pan troglodytes with chronic hepatitis C virus infection following therapeutic silencing of microRNA-122 using SPC3649

ABSTRACT: Chimpanzees with chronic Hepatitis C infection treated with LNA-antimiR-122.

ORGANISM(S): Pan troglodytes

SUBMITTER: Andreas Petri

PROVIDER: E-MEXP-2375 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection.

Lanford Robert E RE Hildebrandt-Eriksen Elisabeth S ES Petri Andreas A Persson Robert R Lindow Morten M Munk Martin E ME Kauppinen Sakari S Ørum Henrik H

Science (New York, N.Y.) 20091203 5962

The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. We found that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA)-modified oligonucleotide (SPC3649) complementary to miR-122 leads to long-lasting suppression of HCV viremia, with no evidence of viral resistance or side effects in the treated animals. Furthermore, t ...[more]

PMID: 19965718

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Project description:Investigation of whole genome gene expression level changes in African Green Monkeys treated with antimiR-33a/b, compared to the animal treated with vehicle The treatment of the monkeys is further described in Rottiers V, Obad S, McGarrah R, Black JC, Lindholm M, Goody R, Lawrence M, Whetstine JR, Gerszten RE, Kauppinen S, NM-CM-$M-CM-$r AM. (2013). Pharmacological inhibition of a microRNA family in non-human primates by a seed-targeting 8-mer antimiR oligonucleotide. Accepted for publication at Science Translational Medicine. MicroRNAs (miRNAs) regulate many aspects of human biology. They target mRNAs for translational repression or degradation through base-pairing with 3M-bM-^@M-^Y UTRs, primarily via seed sequences (nucleotides 2-8 in the mature miRNA sequence). A number of individual miRNAs and miRNA families share seed sequences and targets, but differ in the sequences outside of the seed. miRNAs have been implicated in the etiology of a wide variety of human diseases and therefore represent promising therapeutic targets. However, potential redundancy and compensatory action of different miRNAs sharing the same seed sequence, and the challenge of simultaneously targeting miRNAs that differ significantly in non-seed sequences complicates therapeutic targeting approaches. We recently demonstrated effective inhibition of entire miRNA families using seed-targeting 8-mer locked nucleic acid (LNA)-modified antimiRs in short-term experiments in mammalian cells and in mice. However, the long-term efficacy and safety of this approach in higher organisms, such as humans and non-human primates, has not been determined. Here, we show that pharmacological inhibition of the miR-33 family, key regulators of cholesterol/lipid homeostasis, by a subcutaneously delivered 8-mer LNA-modified antimiR in obese and insulin-resistant non-human primates results in de-repression of miR-33 targets, such as ABCA1, increases circulating high-density lipoprotein-cholesterol (HDL-C), and is well tolerated over 108 days of treatment. These findings demonstrate the efficacy and safety of an 8-mer LNA-antimiR against a miRNA family in a non-human primate metabolic disease model, suggesting that this could be a feasible approach for therapeutic targeting of miRNA families sharing the same seed sequence in human diseases. Expression analysis study in obese Non Human Primates (African Green Monkeys). Five animals treated with antimiR-33a/b were compared to five animals treated with vehicle.

Dataset Information

Transcription profiling of liver from Pan troglodytes with chronic hepatitis C virus infection following therapeutic silencing of microRNA-122 using SPC3649

Publications

Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection.

Similar Datasets

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