GEO series

Atrophin-1 Antisense Oligonucleotide Provides Robust Protection from Pathology in a Fully Humanized DRPLA Model

GSE296072 Mus musculus (mouse) RNA-seq (gene expression) 30 samples Submitted 2025/05/05 Platform GPL13112

At a glance

RNA-seq (gene expression) · mouse · 30 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 30 samples: 30 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA modelMolecular therapy. Nucleic acids · 2026

Summary (written by the submitters)

Dentatorubral-pallidoluysian atrophy (DRPLA) is a fatal neurodegenerative disease arising from a CAG repeat expansion in the atrophin-1 (ATN1) gene. Because DRPLA, like many repeat expansion disorders (REDs), arises predominantly from toxic gain-of-function mechanisms, we hypothesized that ATN1 knockdown would have therapeutic potential.

Read the full summary ↓

To test this, we established the first fully-humanized mouse model of a RED, in which one allele of mouse Atn1 is completely replaced by human ATN1, including 112 pure CAG repeats. This novel approach to exploring RED biology provides significant advantages, notably the ability to test sequence-specific therapeutics targeting human sequences, even in introns and untranslated regions of pre-mRNA. We found that our model—the Atn1Q112/+ mouse—recapitulates key features of human DRPLA, including behavioral alterations, reduced brain size and aggregate accumulation. We treated Atn1Q112/+ mice with antisense oligonucleotides (ASOs) targeting mouse Atn1 (to probe for loss of function concerns), human ATN1, or a combination. Treatment with human, but not mouse, ATN1-targeting ASOs provides remarkable protection from a range of disease-related behavioral phenotypes, including aggregation of mutant ATN1 (mATN1), and marked rescue of transcriptional dysregulation in the cerebellum. These results have helped motivate an ongoing human clinical study of ASOs targeting ATN1 for DRPLA.

Published in

Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA model

Smith VL, Gidi BZ, Bragg RM et al. · Molecular therapy. Nucleic acids 2026 · PMID 41624332 · doi:10.1016/j.omtn.2025.102815

This dataset

Open GSE296072 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, 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, or the whole study as GSE296072_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1257447 and SRA study SRP582490. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41624332) ↗

Study design

30 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 30 sample titles: 30 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8964639 Raw_ID 8, Female, Q112, Saline, Rep 1
GSM8964640 Raw_ID 55, Female, Q112, Saline, Rep 2
GSM8964641 Raw_ID 21, Male, Q112, Saline, Rep 3
GSM8964642 Raw_ID 53, Male, Q112, Saline, Rep 4
GSM8964643 Raw_ID 132, Male, Q112, Saline, Rep 5
GSM8964644 Raw_ID 84, Female, Q112, Mo_ASO, Rep 1
GSM8964645 Raw_ID 115, Female, Q112, Mo_ASO, Rep 2
GSM8964646 Raw_ID 41, Male, Q112, Mo_ASO, Rep 3
GSM8964647 Raw_ID 58, Male, Q112, Mo_ASO, Rep 4
GSM8964648 Raw_ID 116, Male, Q112, Mo_ASO, Rep 5
GSM8964649 Raw_ID 13, Female, Q112, Hu_ASO, Rep 1
GSM8964650 Raw_ID 34, Female, Q112, Hu_ASO, Rep 2
GSM8964651 Raw_ID 15, Male, Q112, Hu_ASO, Rep 3
GSM8964652 Raw_ID 26, Male, Q112, Hu_ASO, Rep 4
GSM8964653 Raw_ID 102, Male, Q112, Hu_ASO, Rep 5
GSM8964654 Raw_ID 7, Female, WT, Saline, Rep 1
GSM8964655 Raw_ID 52, Female, WT, Saline, Rep 2
GSM8964656 Raw_ID 124, Female, WT, Saline, Rep 3
GSM8964657 Raw_ID 20, Male, WT, Saline, Rep 4
GSM8964658 Raw_ID 131, Male, WT, Saline, Rep 5
GSM8964659 Raw_ID 45, Female, WT, Mo_ASO, Rep 1
GSM8964660 Raw_ID 87, Male, WT, Mo_ASO, Rep 2
GSM8964661 Raw_ID 88, Male, WT, Mo_ASO, Rep 3
GSM8964662 Raw_ID 89, Male, WT, Mo_ASO, Rep 4
GSM8964663 Raw_ID 118, Male, WT, Mo_ASO, Rep 5
GSM8964664 Raw_ID 28, Female, WT, Hu_ASO, Rep 1
GSM8964665 Raw_ID 16, Male, WT, Hu_ASO, Rep 2
GSM8964666 Raw_ID 35, Male, WT, Hu_ASO, Rep 3
GSM8964667 Raw_ID 101, Male, WT, Hu_ASO, Rep 4
GSM8964668 Raw_ID 107, Male, WT, Hu_ASO, Rep 5

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.