Evidence map›Paper›PMID 41256007›Full record

ArticleNAR molecular medicine2024

Self-amplifying RNAs generated with the modified nucleotides 5-methylcytidine and 5-methyluridine mediate strong expression and immunogenicity

Hiva Azizi, Tyler M Renner, Gerard Agbayani, Bryan Simard, Renu Dudani, Blair A Harrison, Umar Iqbal, Yimei Jia, Michael J McCluskie, Bassel Akache

Abstract read
In one paragraph

Article in NAR molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Article
  2. Transgene sequence codon optimization and composition determines replication competence of self-amplifying RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. "More" Artificial mRNAs: Beyond the Art of Nature.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Hiva AziziHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Tyler M RennerHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Gerard AgbayaniHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Bryan SimardHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Renu DudaniHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Blair A HarrisonHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Umar IqbalHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Yimei JiaHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Michael J McCluskieHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
Bassel AkacheHuman Health Therapeutics, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.ORCID https://orcid.org/0000-0002-5377-7193

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

When utilized in therapeutic applications, synthetic self-amplifying RNA (saRNA) can lead to higher and more sustained expression than standard messenger RNA (mRNA). 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 saRNA have so far exclusively relied on RNA containing the canonical nucleotides adenosine, cytidine, guanosine and uridine. For the first time, we show that noncanonical nucleotides, such as 5-methylcytidine (m5C) and 5-methyluridine (m5U), are sufficiently compatible with a replicon derived from Venezuelan equine encephalitis alphavirus mediating protein translation

Identifiers

PMID41256007
PMCPMC12429210

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.