GEO series

Depleting prion protein using splice-switching small molecules

GSE330903 Homo sapiens (human) RNA-seq (gene expression) 31 samples Submitted 2026/07/09 Platform GPL34295

At a glance

RNA-seq (gene expression) · human · 31 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: 31 samples: 6 conditions, mostly in duplicateGroups 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: Depleting prion protein using splice-switching small moleculesbioRxiv : the preprint server for biology · 2026

Summary (written by the submitters)

Prion diseases are fatal neurodegenerative disorders driven by prion protein (PrP) misfolding, and lowering cellular PrP represents a promising therapeutic strategy. Here we report a small-molecule approach that reduces PrP by modulating pre-mRNA splicing of the PRNP gene. Through chemical modification of the clinically approved splicing modulator risdiplam, we generated CP3, the first class of compounds that selectively activate a cryptic exon in PRNP and routes its mRNA product for degradation, reducing PrP by ~70% in cells.

Read the full summary ↓

We demonstrate that CP3 activity critically depends on alternative splicing factor Luc7L, revealing a novel requirement for alternative splicing factors in small molecule splicing modulation. Strikingly, co-administration of CP3 with a Luc7L activator PTC258 significantly lowers PrP levels in the brains of transgenic mice. These results establish splicing modulation as a powerful strategy for PrP reduction and highlight the potential of small-molecule cooperativity for therapeutic RNA targeting.

Published in

Depleting prion protein using splice-switching small molecules

Liu B, Fair B, Kuang Z et al. · bioRxiv : the preprint server for biology 2026 · PMID 42395399 · doi:10.64898/2026.06.26.734742

This dataset

Open GSE330903 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 GSE330903_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 PRJNA1465889 and SRA study SRP700378. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42395399) ↗

Study design

6 conditions, mostly in duplicate

LN-229 cells, DMSO vehicle, 24 h, biol ×4 GM12878 cells, DMSO vehicle, 24 h, biol ×4 LN-229 cells, CP3 1000 nM + 25 µM BPN15477 co… ×2 LN-229 cells, CP3 3160 nM + 25 µM BPN15477 co… ×2 LN-229 cells, CP3 316 nM + 25 µM BPN15477 co-… ×2 GM12878 cells, BPN15477 25000 nM, 24 h, biol ×2 LN-229 cells, CP3 10000 nM, 24 h, biol ×1 LN-229 cells, CP3 1000 nM, 24 h, biol ×1 +13 more

Supports a between-group comparison across 16 samples.

How we read this: 6 replicated groups read from 31 sample titles; they account for 16 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

GSM9735446 LN-229 cells, CP3 1000 nM + 25 µM BPN15477 co-treatment, 24 h, biol rep 1 LN-229 cells, CP3 1000 …
GSM9735447 LN-229 cells, CP3 1000 nM + 25 µM BPN15477 co-treatment, 24 h, biol rep 2 LN-229 cells, CP3 1000 …
GSM9735448 LN-229 cells, CP3 3160 nM + 25 µM BPN15477 co-treatment, 24 h, biol rep 1 LN-229 cells, CP3 3160 …
GSM9735449 LN-229 cells, CP3 3160 nM + 25 µM BPN15477 co-treatment, 24 h, biol rep 2 LN-229 cells, CP3 3160 …
GSM9735450 LN-229 cells, CP3 316 nM + 25 µM BPN15477 co-treatment, 24 h, biol rep 1 LN-229 cells, CP3 316 n…
GSM9735451 LN-229 cells, CP3 316 nM + 25 µM BPN15477 co-treatment, 24 h, biol rep 2 LN-229 cells, CP3 316 n…
GSM9735452 LN-229 cells, CP3 10000 nM, 24 h, biol rep 1
GSM9735453 LN-229 cells, CP3 1000 nM, 24 h, biol rep 1
GSM9735454 LN-229 cells, CP3 31600 nM, 24 h, biol rep 1
GSM9735455 LN-229 cells, CP3 3160 nM, 24 h, biol rep 1
GSM9735456 LN-229 cells, CP3 316 nM, 24 h, biol rep 1
GSM9735457 LN-229 cells, DMSO vehicle, 24 h, biol rep 1 LN-229 cells, DMSO vehi…
GSM9735458 LN-229 cells, DMSO vehicle, 24 h, biol rep 2 LN-229 cells, DMSO vehi…
GSM9735459 LN-229 cells, DMSO vehicle, 24 h, biol rep 3 LN-229 cells, DMSO vehi…
GSM9735460 LN-229 cells, DMSO vehicle, 24 h, biol rep 4 LN-229 cells, DMSO vehi…
GSM9735461 LN-229 cells, Risdiplam 10000 nM, 24 h, biol rep 1
GSM9735462 LN-229 cells, Risdiplam 1000 nM, 24 h, biol rep 1
GSM9735463 LN-229 cells, Risdiplam 31600 nM, 24 h, biol rep 1
GSM9735464 LN-229 cells, Risdiplam 3160 nM, 24 h, biol rep 1
GSM9735465 LN-229 cells, Risdiplam 316 nM, 24 h, biol rep 1
GSM9735466 LN-229 cells, SMSM74 10000 nM, 24 h, biol rep 1
GSM9735467 LN-229 cells, SMSM74 1000 nM, 24 h, biol rep 1
GSM9735468 LN-229 cells, SMSM74 31600 nM, 24 h, biol rep 1
GSM9735469 LN-229 cells, SMSM74 3160 nM, 24 h, biol rep 1
GSM9735470 LN-229 cells, SMSM74 316 nM, 24 h, biol rep 1
GSM9735471 GM12878 cells, BPN15477 25000 nM, 24 h, biol rep 1 GM12878 cells, BPN15477…
GSM9735472 GM12878 cells, BPN15477 25000 nM, 24 h, biol rep 2 GM12878 cells, BPN15477…
GSM9735473 GM12878 cells, DMSO vehicle, 24 h, biol rep 1 GM12878 cells, DMSO veh…
GSM9735474 GM12878 cells, DMSO vehicle, 24 h, biol rep 2 GM12878 cells, DMSO veh…
GSM9735475 GM12878 cells, DMSO vehicle, 24 h, biol rep 3 GM12878 cells, DMSO veh…
GSM9735476 GM12878 cells, DMSO vehicle, 24 h, biol rep 4 GM12878 cells, DMSO veh…

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