Data from: Self-amplifying RNA generated with the modified nucleotides 5-methylcytidine and 5-methyluridine mediate strong expression and immunogenicity in vivo
Bibliographic record
Abstract
When utilized in therapeutic applications, synthetic self-amplifying RNA can lead to higher and more sustained expression than standard messenger RNA. This feature is particularly important for gene replacement therapy applications where prolonged expression could reduce the dose and frequency of treatments. The inclusion of modified nucleotides in synthetic non-amplifying mRNA has been shown to increase RNA stability, reduce immune activation and enhance gene expression. Preclinical and clinical studies with self-amplifying RNA (saRNA) have so far exclusively relied on RNA containing the canonical nucleotides adenosine, cytidine, guanosine and uridine. For the first time, we show that non-canonical nucleotides, such as m5C and m5U, are sufficiently compatible with a replicon derived from Venezuelan equine encephalitis alphavirus mediating protein translation in vitro, while those containing m1ψ in place of uridine show no detectable expression. When administered in vivo, saRNA generated with m5C or m5U mediate sustained gene expression of the luciferase reporter gene with those incorporating m5U appearing to lead to more prolonged expression. Finally, distinct antigen-specific humoral and cellular immune responses were induced by modified saRNA encoding the model antigen ovalbumin. The use of modified nucleotides with saRNA-based platforms could enhance their potential to be used effectively in a variety of applications.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".