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

GSE57597 Mus musculus (mouse) Expression microarray 58 samples Submitted 2015/01/01 Platform GPL16570

At a glance

Expression microarray · mouse · 58 samples

What it is: Expression microarrayGene activity read on a chip (the older technology that RNA-seq replaced).
Organism: Mus musculus (mouse)
Samples: 58 samples
Data you can get: A processed expression table (series matrix) and the array files, from NCBI.

Summary (written by the submitters)

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.

Read the full summary ↓

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.

This dataset

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Download · which file do I need?

Direct links to NCBI, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need.

All supplementary files ↗

3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE57597_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Whole study · RAW.tar ↓

What the files usually look like: For arrays the series matrix is normally the normalised expression table you want; the raw array files (CEL and similar) are in the RAW.tar.

Also filed as BioProject PRJNA246752. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 25607839) ↗

Samples in this study

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+ 58 more — browse all 58 samples with per-sample file links →

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