Evidence map›Paper›PMID 29950408›Full record

ArticleJournal of virology2018

Cellular Antisilencing Elements Support Transgene Expression from Herpes Simplex Virus Vectors in the Absence of Immediate Early Gene Expression.

Fang Han, Yoshitaka Miyagawa, Gianluca Verlengia, Selene Ingusci, Marie Soukupova, Michele Simonato, Joseph C Glorioso, Justus B Cohen

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Next-generation replication-defective HSV vectors for delivery of large DNA payloads.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  3. Review
  4. Viral and cellular insulators promote sustained HSV vector-mediated transgene expression in brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. [AttenuatedNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021
    Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Gene Therapy Tools for Brain Diseases.Frontiers in pharmacology · 2019
    Review
  15. 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

8 authors at 3 institutions in 3 countries.

Fang HanSchool of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
Yoshitaka MiyagawaDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Gianluca VerlengiaSection of Pharmacology, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Selene IngusciSection of Pharmacology, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Marie SoukupovaSection of Pharmacology, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Michele SimonatoSection of Pharmacology, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Joseph C GloriosoDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Justus B CohenDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA jbc@pitt.edu.ORCID https://orcid.org/0000-0003-1208-1883
University of Pittsburgh · USUniversity of Ferrara · ITVita-Salute San Raffaele University · IT

Funding

PRE-CLINICAL VECTOR PRODUCTIONP01DK044935 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GOINS, WILLIAM F. · 1993 to 2010
$11.8M
Glycine Receptor Expression in Sensory Afferents to Modulate Pain SignalingR01NS064988 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLORIOSO, JOSEPH C · 2011 to 2015
$1.8M
NIDDK NIH HHS P01 DK044935NINDS NIH HHS R01 NS064988
6 · The paper itself

Abstract

Inactivation of all herpes simplex virus (HSV) immediate early (IE) genes to eliminate vector cytotoxicity results in rapid silencing of the viral genome, similar to the establishment of HSV latency. We recently reported that silencing of a nonviral reporter cassette could be overcome in nonneuronal cells by positioning the cassette in the viral latency (LAT) locus between resident chromatin boundary elements. Here, we tested the abilities of the chicken hypersensitive site 4 insulator and the human ubiquitous chromatin opening element A2UCOE to promote transgene expression from an IE-gene-inactivated HSV vector. We found that A2UCOE was particularly active in nonneuronal cells and reduced reporter promoter occupancy by a repressive histone mark. We determined whether multiple transgenes could be expressed under the control of different promoters from different loci of the same virus. The results showed abundant coexpression of LAT-embedded and A2UCOE-flanked genes in nonneuronal cells. In addition, a third reporter gene without known protective elements was active in cultured rat sensory neurons. These findings indicate that cellular antisilencing sequences can contribute to the expression of multiple genes from separate promoters in fully IE gene-disabled HSV vectors, providing an opportunity for therapeutic applications requiring mutually independent expression of different gene products from a single vector.

Indexed as

Genetic VectorsAnimalsChickensDNA, ViralGenes, Immediate-EarlyGenes, ViralGenetic TherapyGenome, ViralHerpes SimplexHerpesvirus 1, HumanHumansPromoter Regions, GeneticTransgenesVirus InactivationVirus LatencyDNA, Viralchromatin remodelingcHS4CTCFgene therapyHSV-1ICP0insulatortransgene expressionUCOEviral vector

Identifiers

PMID29950408
PMCPMC6096828
OpenAlexW2811062911

What OpenQuestion holds

Textmetadata
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.