Evidence map›Paper›PMID 28877647›Full record

ArticleHuman gene therapy2017

Improvement of In Vivo Expression of Genes Delivered by Self-Amplifying RNA Using Vaccinia Virus Immune Evasion Proteins.

Tim Beissert, Lars Koste, Mario Perkovic, Kerstin C Walzer, Stephanie Erbar, Abderraouf Selmi, Mustafa Diken, Sebastian Kreiter, Özlem Türeci, Ugur Sahin

Open access · bronzeAbstract read
In one paragraph

Article in Human gene therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
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

49 citing papers in PubMed, 76 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  13. Article
  14. Alphaviral backbone of self-amplifying RNA enhances protein expression and immunogenicity against SARS-CoV-2 antigen.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  15. Article
  16. Molecular therapy. Nucleic acids · 2024
    Article
  17. Molecular therapy. Nucleic acids · 2024
    Article
  18. Article
  19. Article
  20. Article
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 at 1 institution in 1 country.

Tim Beissert1 TRON-Translational Oncology , Mainz, Germany .
Lars Koste2 III Medical Clinic at the University Medical Center of the Johannes Gutenberg University Mainz , Mainz, Germany .
Mario Perkovic1 TRON-Translational Oncology , Mainz, Germany .
Kerstin C Walzer3 BioNTech AG , Mainz, Germany .
Stephanie Erbar4 BioNTech RNA Pharmaceuticals GmbH , Mainz, Germany .
Abderraouf Selmi1 TRON-Translational Oncology , Mainz, Germany .
Mustafa Diken1 TRON-Translational Oncology , Mainz, Germany .
Sebastian Kreiter1 TRON-Translational Oncology , Mainz, Germany .
Özlem Türeci5 CI3-Cluster for Individualized Immune Intervention , Mainz, Germany .
Ugur Sahin1 TRON-Translational Oncology , Mainz, Germany .
BioNTech (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Among nucleic acid-based delivery platforms, self-amplifying RNA (saRNA) vectors are of increasing interest for applications such as transient expression of recombinant proteins and vaccination. saRNA is safe and, due to its capability to amplify intracellularly, high protein levels can be produced from even minute amounts of transfected templates. However, it is an obstacle to full exploitation of this platform that saRNA induces a strong innate host immune response. In transfected cells, pattern recognition receptors sense double-stranded RNA intermediates and via activation of protein kinase R (PKR) and interferon signaling initiate host defense measures including a translational shutdown. To reduce pattern recognition receptor stimulation and unleash suppressed saRNA translation, this study co-delivered non-replicating mRNA encoding vaccinia virus immune evasion proteins E3, K3, and B18. It was shown that E3 is far superior to K3 or B18 as a highly potent blocker of PKR activation and of interferon (IFN)-β upregulation. B18, in contrast, is superior in controlling OAS1, a key IFN-inducible gene involved in viral RNA degradation. By combining all three vaccinia proteins, the study achieved significant suppression of PKR and IFN pathway activation in vitro and enhanced expression of saRNA-encoded genes of interest both in vitro and in vivo. This approach promises to overcome key hurdles of saRNA gene delivery. Its application may improve the bioavailability of the encoded protein, and reduce the effective dose and correspondingly the cost of goods of manufacture in the various fields where saRNA utilization is envisioned.

Indexed as

Gene ExpressionGenetic VectorsGene Transfer TechniquesImmune EvasionRNAViral ProteinsAnimalsCell LineeIF-2 KinaseFemaleHumansMiceMice, Inbred BALB CVaccinia viruseIF-2 Kinaseprotein kinase R, mouseRNAViral Proteinsalphavirusrepliconself-amplifying RNAvaccinia virus B18vaccinia virus E3vaccinia virus K3

Identifiers

PMID28877647
PMCPMC5737720
OpenAlexW2753406470

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.