GEO series

CNS-Targeted Base Editing of the Major Late-Onset Tay-Sachs Mutation Alleviates Disease in Mice

GSE268712 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/06/02 Platform GPL24247

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: 4 × Brain, AAV ABE, vs 4 × Brain, AAV GFP, vs 4 × Brain, WT Control,Groups 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)

Late-onset Tay-Sachs (LOTS) disease is a lysosomal storage disorder most commonly caused by a point mutation (c.805G>A) in the HEXA gene encoding the α-subunit of the lysosomal enzyme β-hexosaminidase A. LOTS manifests as a range of gradually worsening neurological symptoms beginning in young adulthood. Here, we explored the efficacy of an adenine base editor (ABE) programmed with a small guide RNA (sgRNA) to correct the HEXA c.805G>A mutation.

Read the full summary ↓

Base editing in LOTS patient fibroblasts successfully converted the pathogenic HEXA c.805A to G and partially restored β-hexosaminidase activity, with minimal genome-wide off-target editing. We generated a LOTS mouse model in which the mice exhibited decreased β-hexosaminidase activity, accumulation of GM2 ganglioside in the brain, progressive neurological manifestations, and reduced lifespan. Treatment of LOTS mice with the neurotropic virus AAV-PHP.eB carrying the ABE and an sgRNA targeting the LOTS point mutation partially corrected the c.805G>A mutation in the CNS, significantly increased brain β-hexosaminidase activity, and substantially reduced GM2 ganglioside accumulation in the brain. Moreover, the therapy delayed symptom onset and significantly extended median lifespan. These findings highlight the potential of base editing as an effective treatment for LOTS and its broader applicability to other lysosomal storage disorders.

This dataset

Open GSE268712 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 GSE268712_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 PRJNA1118306 and SRA study SRP510879. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

4 × Brain, AAV ABE, vs 4 × Brain, AAV GFP, vs 4 × Brain, WT Control,

Supports a between-group comparison across 12 samples.

How we read this: 3 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

GSM8297337 Brain, AAV ABE, rep1 Brain, AAV ABE,
GSM8297338 Brain, AAV ABE, rep2 Brain, AAV ABE,
GSM8297339 Brain, AAV ABE, rep3 Brain, AAV ABE,
GSM8297340 Brain, AAV ABE, rep4 Brain, AAV ABE,
GSM8297341 Brain, AAV GFP, rep1 Brain, AAV GFP,
GSM8297342 Brain, AAV GFP, rep2 Brain, AAV GFP,
GSM8297343 Brain, AAV GFP, rep3 Brain, AAV GFP,
GSM8297344 Brain, AAV GFP, rep4 Brain, AAV GFP,
GSM8297345 Brain, WT Control, rep1 Brain, WT Control,
GSM8297346 Brain, WT Control, rep2 Brain, WT Control,
GSM8297347 Brain, WT Control, rep3 Brain, WT Control,
GSM8297348 Brain, WT Control, rep4 Brain, WT Control,

Datasets on a similar topic

GSE248791 Macrophage-based delivery of interleukin-10 alleviates atherosclerosis 18 samples shares alleviates, base
GSE295426 Targeting branched-chain amino acids alleviates pulmonary fibrosis [RNA-seq] 54 samples shares alleviates
GSE261300 Roxadustat alleviates metabolic traits in letrozole-induced PCOS mice 39 samples shares alleviates
GSE307127 Immune Receptor Lag3 Deletion Alleviates Neurodegeneration Phenotypes in a Mouse Model of Alzheimer’s Disease 36 samples shares alleviates
GSE294777 Early Intervention of the PKC-Hippo Signaling Alleviates Post-Traumatic Osteoarthritis 36 samples shares alleviates
GSE288803 Proteasome inhibition alleviates proteinuria in Lmx1b knock-in mice with dysfunctional LIM domains 35 samples shares alleviates
GSE342666 Sodium oxybate, a narcolepsy therapeutic, remodels the gut microbiota and alleviates metabolic dysfunction in developing and established obesity 32 samples shares alleviates
GSE267450 Loss of Nuclear Receptor Nr4a3 Alleviates Cellular Senescence to Promote Adult Direct Cardiac Reprogramming (RNA-Seq) 30 samples shares alleviates

Search all mouse RNA-seq datasets in GEO →

Share this dataset

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.