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Tuning siRNA Specificity through Seed Region Incorporation of Deoxyribonucleotide Stereoisomers

GSE313756 Homo sapiens (human) RNA-seq (gene expression) 104 samples Submitted 2026/02/01 Platform GPL24247Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 104 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
104 samples
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)
Precise chemical design continues to drive advances in RNA-based therapeutics. Here, we report the synthesis and site-specific incorporation of four canonical phosphoramidites (U, C, A, and G), each bearing non-natural nucleoside configurations: β-D-2′-deoxyxylonucleosides and α-L-2′-deoxyribonucleosides. These stereochemically distinct nucleoside analogs were introduced at positions 6 and 7 within siRNA seed regions.
Read the full summary ↓
When applied to siRNAs targeting Ttr, ACTN1, and Marc1, these modifications reduced off-target gene repression in functional assays and, in several cases, in transcriptome-wide differential expression analyses, while preserving robust on-target activity. In vivo, Marc1-targeting siRNAs containing these modified nucleosides showed decreased hepatotoxicity, as evidenced by reduced serum ALT and AST levels. Collectively, these findings establish β-D-2′-deoxyxylonucleoside and α-L-2′-deoxyribonucleoside analogs as promising chemical tools for enhancing the specificity and safety of siRNA therapeutics. This work underscores the power of integrating rational nucleoside design with comprehensive functional and in vivo evaluation to advance drug development based on RNA interference (RNAi).
This dataset
Open GSE313756 in finder → Find more 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 GSE313756_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 PRJNA1381542 and SRA study SRP655264. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Samples in this study

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