GEO series
Engineered circular RNA compatible with complete nucleoside modification and rolling circle translation through a Cap-independent translation enhancer (CITE)
GSE303451
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
16 samples
Submitted 2026/02/28
Platform GPL24676Platform GPL24247
Summary
Circular RNAs (circRNAs) exhibit extended stability and enhanced,sustained protein expression. Nucleoside modification and rolling circle translation are supposed to reduce the immunogenicity and enhance the translational efficiency of circRNAs. However, it remains challenging to produce encodable circRNAs with modified nucleosides rather than the original nucleosides. Here, we identified a 39-nucleotide Cap-independent Translation Enhancer (CITE) element, termed BBV, which effectively drove the translation of nucleoside-modified RNAs with minimal immunogenicity. Subsequently, we demonstrated that the in vivo-produced circRNA harboring BBV could achieve efficient and sustained rolling circle translation lasting two weeks. Furthermore, we developed an extracellular vesicle-based delivery platform, termed EPM-EABR ASsisted Vesicle Yield (EASY), to deliver circRNAs without introducing viral Gag-Pol proteins. Additionally, we developed a Permuted Intron for Clean CircRNAs (PICC) system to produce scarless circRNAs via in vitro transcription and achieved efficient rolling circle translation driven by BBV. In a murine model, we demonstrated that the PICC-produced circRNA vaccine outperformed the N1mψ-mRNA vaccine in inducing anti-tumor immunity. Importantly, we succeeded to achieve complete substitution with modified nucleosides in circRNAs via Twister ribozyme self-cleaving, dramatically reducing the immunogenicity of circRNAs, but still retaining the ability of rolling circle translation. Collectively, we established a nucleoside-modified circRNA platform that facilitates efficient translation with minimal immunogenicity, offering a safer and more effective platform for applications in vaccine development and disease treatment.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE303451_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 16 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1295446 and SRA study SRP603021. Searching any of these in the dataset finder brings you back here.
Study design
6 conditions, mostly in triplicate
A549, mock, ×3
A549, unmodified circRNA, ×3
A549, modified circRNA, ×3
Tumor, circRNA, ×3
Tumor, PBS, ×2
Tumor, mRNA, ×2
Supports a case/control comparison: 7 samples read as cases, 3 as controls.
6 replicated groups read from 16 sample titles; they account for 16 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9126976 A549, mock, rep1
- GSM9126977 A549, mock, rep2
- GSM9126978 A549, mock, rep3
- GSM9126979 A549, unmodified circRNA, rep1
- GSM9126980 A549, unmodified circRNA, rep2
- GSM9126981 A549, unmodified circRNA, rep3
- GSM9126982 A549, modified circRNA, rep1
- GSM9126983 A549, modified circRNA, rep2
- GSM9126984 A549, modified circRNA, rep3
- GSM9126985 Tumor, PBS, rep1
- GSM9126986 Tumor, PBS, rep2
- GSM9126987 Tumor, mRNA, rep1
- GSM9126988 Tumor, mRNA, rep2
- GSM9126989 Tumor, circRNA, rep1
- GSM9126990 Tumor, circRNA, rep2
- GSM9126991 Tumor, circRNA, rep3
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