GEO series

AAV-mediated gene therapy demonstrates phenotypic rescue in a mouse model of Cockayne Syndrome

GSE336535 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2026/06/25 Platform GPL34328

At a glance

RNA-seq (gene expression) · mouse · 12 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: 12 samples: 3 × KO_F vs 3 × Het_F vs 3 × KO_M vs 3 × Het_MGroups 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.

Summary (written by the submitters)

Cockayne Syndrome (CS) is an autosomal recessive, progressive developmental and neurodegenerative disease. Approximately 30% of cases are caused by mutations in the ERCC8/CSA gene. Patients with CS present with cutaneous photosensitivity, growth failure, shorter life span, and a progressive degeneration of the central nervous system. Loss-of-function mutations in CSA result in deficiencies in the transcription-coupled nucleotide excision repair (TC-NER).

Read the full summary ↓

Currently, no therapies are available for these patients. Adeno-associated virus (AAV)-mediated gene therapy offers an opportunity to address this unmet need. We designed a new AAV vector encoding human CSA under a ubiquitous promoter. We tested the therapeutic efficacy of this AAV9-CSA vector by neonatal intracerebroventicular injection in the Csa-/-;Xpa-/- mouse model. Treatment with AAV9-CSA resulted in a significant increase in lifespan, and broad distribution of human CSA in the brain and heart, without evidence of vector‑related toxicity. Despite clear therapeutic benefit, we also observed neuroradiological abnormalities, and neuropathologic alterations, including hypomyelination, astrocytosis, and microgliosis, as well as likely life-limiting transcriptomic alterations in liver at endpoint. Nonetheless, the success of these experiments paves the way for the first clinical translation of an AAV gene therapy for CS patients into humans.

This dataset

Open GSE336535 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 GSE336535_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 PRJNA1481944 and SRA study SRP712521. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

3 × KO_F vs 3 × Het_F vs 3 × KO_M vs 3 × Het_M

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. 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

GSM9837054 KO_F_108 KO_F
GSM9837055 Het_F_111 Het_F
GSM9837056 KO_F_112 KO_F
GSM9837057 Het_F_115 Het_F
GSM9837058 KO_M_118 KO_M
GSM9837059 Het_M_119 Het_M
GSM9837060 KO_M_122 KO_M
GSM9837061 KO_F_123 KO_F
GSM9837062 Het_M_125 Het_M
GSM9837063 Het_F_126 Het_F
GSM9837064 KO_M_136 KO_M
GSM9837065 Het_M_137 Het_M

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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.