GEO series

Discovery of Long-Acting APOC3 siRNA for Treating Patients with Hypertriglyceridemia

GSE278574 Homo sapiens (human) RNA-seq (gene expression) 52 samples Submitted 2025/09/25 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 52 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: Homo sapiens (human)
Samples: 52 samples: 52 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: Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemiaNucleic acids research · 2025

Summary (written by the submitters)

Apolipoprotein C-III (APOC3) plays a crucial role in triglyceride metabolism, and its high expression leads to hypertriglyceridemia, a condition associated with an increased risk of cardiovascular disease and acute pancreatitis. However, loss-of-function variants in APOC3 are linked to lower triglyceride levels and reduced incidence of coronary artery diseases.

Read the full summary ↓

APOC3 mRNA, primarily synthesized by hepatocytes, is an ideal target for GalNAc-conjugated small interference RNA (siRNA) mediated gene silencing. Our research takes a unique approach, conducting systematic structure-activity relationship (SAR) studies to identify a long-acting APOC3 siRNA with a minimal number of 2’-F nucleotides. We evaluated the use of 5’-vinylphosphonate (5’-VP), 5’-methylene phosphonate (5’-MP), FHNA, and methane sulphonyl phosphoramidite backbone chemistry in APOC3 siRNA design and employed deoxynucleotides or 2’-O-methyl (OMe) to replace 2’-F residues. Additionally, we utilized 2’-O-methoxyethyl (MOE) nucleotides in conjunction with phosphorothioate modification to enhance metabolic stability. To ensure the preferential loading of the antisense strand, we strategically placed MOE nucleotides at specific sites in the antisense strand. These efforts led to the identification of APOC3 siRNA containing a novel chemical scaffold with a long duration of action (DOA) and tolerability in rodents and nonhuman primates. A comparative analysis of preclinical and clinical data of plozasiran surrogate suggests that our APOC3 siRNA may provide clinical benefits with less frequent exposure (>6 months apart), which could significantly improve the treatment of patients with hypertriglyceridemia.

Published in

Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia

Prakash TP, Mullick AE, Riney S et al. · Nucleic acids research 2025 · PMID 41163544 · doi:10.1093/nar/gkaf1063

This dataset

Open GSE278574 in finder → Find more human 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 GSE278574_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 PRJNA1167806 and SRA study SRP536116. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41163544) ↗

Study design

52 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 52 sample titles: 52 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

GSM8549503 170297, primary hepatocytes, ASO#26, 0.00256 nM, rep1
GSM8549504 170352, primary hepatocytes, ASO#26, 0.00256 nM, rep2
GSM8549505 170477, primary hepatocytes, ASO#26, 0.01280 nM, rep1
GSM8549506 170562, primary hepatocytes, ASO#26, 0.01280 nM, rep2
GSM8549507 170325, primary hepatocytes, ASO#26, 0.06400 nM, rep1
GSM8549508 170353, primary hepatocytes, ASO#26, 0.06400 nM, rep2
GSM8549509 170516, primary hepatocytes, ASO#26, 0.32000 nM, rep1
GSM8549510 170560, primary hepatocytes, ASO#26, 0.32000 nM, rep2
GSM8549511 170296, primary hepatocytes, ASO#26, 1.60000 nM, rep1
GSM8549512 170609, primary hepatocytes, ASO#26, 1.60000 nM, rep2
GSM8549513 170337, primary hepatocytes, ASO#26, 1000.00000 nM, rep1
GSM8549514 170420, primary hepatocytes, ASO#26, 1000.00000 nM, rep2
GSM8549515 170343, primary hepatocytes, ASO#26, 200.00000 nM, rep1
GSM8549516 170371, primary hepatocytes, ASO#26, 200.00000 nM, rep2
GSM8549517 170272, primary hepatocytes, ASO#26, 40.00000 nM, rep1
GSM8549518 170405, primary hepatocytes, ASO#26, 40.00000 nM, rep2
GSM8549519 170266, primary hepatocytes, ASO#26, 5000.00000 nM, rep1
GSM8549520 170331, primary hepatocytes, ASO#26, 5000.00000 nM, rep2
GSM8549521 170389, primary hepatocytes, ASO#26, 8.00000 nM, rep1
GSM8549522 170500, primary hepatocytes, ASO#26, 8.00000 nM, rep2
GSM8549523 170271, primary hepatocytes, ASO#26, 0.00256 nM, rep1
GSM8549524 170569, primary hepatocytes, ASO#26, 0.00256 nM, rep2
GSM8549525 170450, primary hepatocytes, ASO#26, 0.01280 nM, rep1
GSM8549526 170501, primary hepatocytes, ASO#26, 0.01280 nM, rep2
GSM8549527 170511, primary hepatocytes, ASO#26, 0.06400 nM, rep1
GSM8549528 170532, primary hepatocytes, ASO#26, 0.06400 nM, rep2
GSM8549529 170393, primary hepatocytes, ASO#26, 0.32000 nM, rep1
GSM8549530 170495, primary hepatocytes, ASO#26, 0.32000 nM, rep2
GSM8549531 170269, primary hepatocytes, ASO#26, 1.60000 nM, rep1
GSM8549532 170311, primary hepatocytes, ASO#26, 1.60000 nM, rep2
GSM8549533 170584, primary hepatocytes, ASO#26, 1000.00000 nM, rep1
GSM8549534 170611, primary hepatocytes, ASO#26, 1000.00000 nM, rep2
GSM8549535 170449, primary hepatocytes, ASO#26, 200.00000 nM, rep1
GSM8549536 170564, primary hepatocytes, ASO#26, 200.00000 nM, rep2
GSM8549537 170423, primary hepatocytes, ASO#26, 40.00000 nM, rep1
GSM8549538 170441, primary hepatocytes, ASO#26, 40.00000 nM, rep2
GSM8549539 170360, primary hepatocytes, ASO#26, 5000.00000 nM, rep1
GSM8549540 170503, primary hepatocytes, ASO#26, 5000.00000 nM, rep2
GSM8549541 170402, primary hepatocytes, UTC, 8.00000 nM, rep1
GSM8549542 170481, primary hepatocytes, UTC, 8.00000 nM, rep2

+ 12 more — browse all 52 samples with per-sample file links →

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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.