Evidence map›Paper›PMID 36958764›Full record

ArticleJournal for immunotherapy of cancer2023

Adaptation of transgene mRNA translation boosts the anticancer efficacy of oncolytic HSV1.

Huy-Dung Hoang, Aida Said, Nasana Vaidya, Victoria H Gilchrist, Kyle Malone, Usha Kabilan, Serena Topshee, Xiao Xiang, An-Dao Yang, David Olagnier and 6 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 21% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
  3. 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

16 authors at 7 institutions in 3 countries.

Huy-Dung HoangChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Aida SaidChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Nasana VaidyaDepartment Immunology, University of Toronto, Toronto, Ontario, Canada.
Victoria H GilchristChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Kyle MaloneChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Usha KabilanChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Serena TopsheeChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Xiao XiangChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
An-Dao YangChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
David OlagnierDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Karen MossmanDepartment of Medicine, McMaster University, Hamilton, Ontario, Canada.
Shawn T BeugChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Seyed Mehdi JafarnejadPatrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.
Samuel T WorkenheDepartment of Pathobiology, University of Guelph, Guelph, Ontario, Canada.ORCID 0000-0001-9521-3903
Tyson E GraberChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Tommy AlainChildren's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada tommy@arc.cheo.ca.ORCID 0000-0002-0396-9138
University of Ottawa · CAChildren's Hospital of Eastern Ontario · CAAarhus University · DKMcMaster University · CAQueen's University Belfast · GBUniversity of Guelph · CAUniversity of Toronto · CA

Funding

CIHR
6 · The paper itself

Abstract

backgroundTransgenes deliver therapeutic payloads to improve oncolytic virus immunotherapy. Transgenes encoded within oncolytic viruses are designed to be highly transcribed, but protein synthesis is often negatively affected by viral infection, compromising the amount of therapeutic protein expressed. Studying the oncolytic herpes simplex virus-1 (HSV1), we found standard transgene mRNAs to be suboptimally translated in infected cells.

methodsUsing RNA-Seq reads, we determined the transcription start sites and 5'leaders of HSV1 genes and uncovered the US11 5'leader to confer superior activity in translation reporter assays. We then incorporated this 5'leader into GM-CSF expression cassette in oncolytic HSV1 and compared the translationally adapted oncolytic virus with the conventional, leaderless, virus

resultsInclusion of the US11 5'leader in the GM-CSF transgene incorporated into HSV1 boosted translation

conclusionsOur study demonstrates the therapeutic value of identifying and integrating platform-specific

Indexed as

Herpesvirus 1, HumanOncolytic VirusesAnimalsGranulocyte-Macrophage Colony-Stimulating FactorMiceProtein BiosynthesisTransgenesGranulocyte-Macrophage Colony-Stimulating FactorOncolytic Viruses

Identifiers

PMID36958764
PMCPMC10040010
OpenAlexW4360613262

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.