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Series GSE39129 Query DataSets for GSE39129
Status Public on Jul 05, 2013
Title A TLR- and non-TLR-mediated innate response to lentiviruses restricts hepatocyte entry and can be ameliorated by pharmacological blockade
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Lentiviral vector (LV)-mediated gene transfer is a promising method of gene therapy. We previously reported that systemic injection of LV triggers a transient inflammatory response. Here, we carried out studies to better characterize this response, and to develop a strategy to overcome the effects of interferon (IFN) on LV-mediated gene transfer. We profiled gene expression in the liver after LV administration using deep-sequencing, and identified several innate response pathways. We examined the response to LV in MyD88-TRIF knock-out mice, which are incapable of toll-like receptor (TLR) signaling. The IFN response to LV was not reduced in the liver, indicating that a non-TLR pathway can recognize LV in this tissue. Indeed, blocking reverse-transcription with AZT reduced the IFN response only in the liver, suggesting that proviral DNA can be a trigger. To block the inflammatory response, we pre-treated mice with a short-course of dexamethasone. At 4 hours post-treatment, all of the IFN-induced genes were normalized. By blocking the inflammatory response, hepatocyte transduction was dramatically increased, which doubled the level of human factor-IX produced by a hepatocyte-specific LV. Our studies uncover new insights into LV-induced immune responses in the liver, and provide a means to increase the safety and efficiency of LV-mediated gene transfer.
Overall design mRNA profiles from livers of untreated and LV-treated mice were generated by deep-sequencing in Illumina HiSeq 2000.
Contributor(s) Brown BD, Agudo J
Citation(s) 22871668
Submission date Jul 05, 2012
Last update date May 15, 2019
Contact name Brian Brown
Organization name Icahn School of Medicine at Mount Sinai
Department Genetics and Genomic Sciences
Street address 1470 Madison Avenue
City New York
State/province NY
ZIP/Postal code 10029
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (6)
GSM956517 Liver + LV, rep1
GSM956518 Liver + LV, rep2
GSM956519 Liver + LV, rep3
BioProject PRJNA170059
SRA SRP014029

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Supplementary file Size Download File type/resource
GSE39129_Liver+LV_consolidated.txt.gz 74.7 Kb (ftp)(http) TXT
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