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Long-acting STK25 antisense oligonucleotide as a therapeutic candidate for MASLD

GSE308862 Mus musculus (mouse) Single-nucleus RNA-seq 15 samples Submitted 2025/09/28 Platform GPL24247
At a glance

Single-nucleus RNA-seq · mouse · 15 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
15 samples: 5 conditions, mostly in triplicateGroups 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)
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder worldwide and a leading cause of liver-related morbidity. Insulin resistance and hepatic lipid metabolism dysfunction are recognized as central pathological mechanisms, yet no therapy is currently approved specifically for MASLD.
Read the full summary ↓
Antisense oligonucleotides (ASOs) are single-stranded nucleotide drugs with high target specificity and long-lasting activity, making them well suited for chronic metabolic diseases. Here, we describe a novel ASO candidate targeting serine/threonine kinase 25 (STK25), a lipid droplet–associated kinase implicated in MASLD pathogenesis. In three human cell lines, the ASO (c337) robustly reduced STK25 expression. For in vivo validation, we generated Gc337 by GalNAc conjugation to enable liver-specific delivery. In a high-fat diet-induced MASLD mouse model, Gc337 significantly improved insulin sensitivity, reduced hepatic lipid accumulation, and lowered body weight, with efficacy comparable to resmetirom, the only FDA-approved therapy for metabolic-associated steatohepatitis. A single injection sustained >50% hepatic Stk25 knockdown for 35 days without hepatotoxicity, underscoring its long-acting therapeutic profile. Importantly, c337 was designed to avoid all known single-nucleotide polymorphisms (SNPs), ensuring efficacy across genetically diverse populations. Together, these findings establish Gc337 as a durable, SNP-aware, and clinically translatable nucleic acid–based therapeutic candidate for MASLD.
This dataset
Open GSE308862 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 GSE308862_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1333296 and SRA study SRP625507. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
5 conditions, mostly in triplicate
SD–NS ×3 HFD-NS ×3 HFD-338 ×3 HFD-337 ×3 HFD-Res ×3

Supports a between-group comparison across 15 samples.

How we read this: 5 replicated groups read from 15 sample titles; they account for 15 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
Datasets on a similar topic

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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.