Evidence map›Paper›PMID 28365028›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017

Sequence-Modified Antibiotic Resistance Genes Provide Sustained Plasmid-Mediated Transgene Expression in Mammals.

Jiamiao Lu, Feijie Zhang, Andrew Z Fire, Mark A Kay

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Genetic and Molecular Quality Control of Genetically Engineered Mice.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. DNA Vaccines-How Far From Clinical Use?International journal of molecular sciences · 2018
    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

4 authors at 1 institution in 1 country.

Jiamiao LuDepartment of Pediatrics, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Feijie ZhangDepartment of Pediatrics, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Andrew Z FireDepartment of Genetics, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Mark A KayDepartment of Pediatrics, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Palo Alto, CA 94305, USA. Electronic address: markay@stanford.edu.
Stanford University · US

Funding

HEPATIC GENE TRANSFER FOR TREATMENT OF HEMOPHILIAS A &BR01HL064274 · NHLBI · STANFORD UNIVERSITY · PI Mark A Kay · 2000 to 2026
$13.6M
NHLBI NIH HHS R01 HL064274
6 · The paper itself

Abstract

Conventional plasmid vectors are incapable of achieving sustained levels of transgene expression in vivo even in quiescent mammalian tissues because the transgene expression cassette is silenced. Transcriptional silencing results from the presence of the bacterial plasmid backbone or virtually any DNA sequence of >1 kb in length placed outside of the expression cassette. Here, we show that transcriptional silencing can be substantially forestalled by increasing the An/Tn sequence composition in the plasmid bacterial backbone. Increasing numbers of An/Tn sequences increased sustained transcription of both backbone sequences and adjacent expression cassettes. In order to recapitulate these expression profiles in compact and portable plasmid DNA backbones, we engineered the standard kanamycin or ampicillin antibiotic resistance genes, optimizing the number of An/Tn sequence without altering the encoded amino acids. The resulting vector backbones yield sustained transgene expression from mouse liver, providing generic DNA vectors capable of sustained transgene expression without additional genes or mammalian regulatory elements.

Indexed as

alpha 1-AntitrypsinAmpicillinAnimalsAnti-Bacterial AgentsDependovirusDrug Resistance, MicrobialFemaleGene SilencingGenetic EngineeringGenetic VectorsHumansKanamycinLiverMiceMice, Inbred C57BLNucleotide Motifsalpha 1-AntitrypsinAmpicillinAnti-Bacterial AgentsKanamycinantibiotic resistance geneAn/Tn tractsnon-coding transcriptionnucleosomesplasmid silencingplasmid vector

Identifiers

PMID28365028
PMCPMC5417794
OpenAlexW2562311664

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.