Evidence map›Paper›PMID 15194784›Full record

ArticleJournal of virology2004

Antisense-mediated inhibition of human immunodeficiency virus (HIV) replication by use of an HIV type 1-based vector results in severely attenuated mutants incapable of developing resistance.

Xiaobin Lu, Qiao Yu, Gwendolyn K Binder, Ziping Chen, Tatiana Slepushkina, John Rossi, Boro Dropulic

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00131560 (A Phase II, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, and Biological Activity of Single and Repeated Doses of Autologous T Cells Transduced With VRX496 in HIV-Positive Subjects), which is not on this map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.7field-weighted citation impact, top 9% 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.

NCT00131560 phase2unknown statusnot on this mapstarted 2005, after this paper: background citation

A Phase II, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, and Biological Activity of Single and Repeated Doses of Autologous T Cells Transduced With VRX496 in HIV-Positive Subjects

TypeinterventionalSponsorVIRxSYS CorporationRan2005 to 2023Enrolled60ConditionsHIV InfectionArmsVRX496-Modified Autologous T cells
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 89 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Engineering T Cells to Functionally Cure HIV-1 Infection.Molecular therapy : the journal of the American Society of Gene Therapy · 2015
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. HIV-1 reverse transcription.Cold Spring Harbor perspectives in medicine · 2012
    Review
  19. Novel cell and gene therapies for HIV.Cold Spring Harbor perspectives in medicine · 2012
    Review
  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

7 authors at 2 institutions in 1 country.

Xiaobin LuVIRxSYS Corporation, Gaithersburg, MD 20877, USA.
Qiao Yu
Gwendolyn K Binder
Ziping Chen
Tatiana Slepushkina
John Rossi
Boro Dropulic
Ansys (United States) · USCity Of Hope National Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have constructed a human immunodeficiency virus type 1 (HIV-1)-based lentiviral vector expressing a 937-base antisense sequence against the HIV-1 envelope gene. Transduction of CD4(+) T lymphocytes with this vector results in expression of the therapeutic antisense sequence and subsequent inhibition of productive HIV-1 replication. In this report, we examined the effect of antisense-mediated suppression on the potential development of virus escape mutants using a permissive T-cell line cultured under conditions that over serial passages specifically allowed for generation and amplification of mutants selected for by antisense pressure. In the resulting virus clones, we found a significant increase in the number of deletions at the envelope target region (91% compared to 27.5% in wild-type HIV). Deletions were most often greater than 1 kb in length. These data demonstrate for the first time that during antisense-mediated suppression of HIV, mutants develop as a direct result of selective pressure on the HIV genomic RNA. Interestingly, in clones where deletions were not observed, there was a high rate of A-G transitions in mutants at the antisense target region but not outside this region, which is consistent with those mutations that are predicted as a result of antisense-mediated modification of double-stranded RNA by the enzyme double-stranded RNA-specific adenosine deaminase. These clones were not found to be escape mutants, as their replicative ability was severely attenuated, and they did not replicate in the presence of vector.

Indexed as

Genetic VectorsBase SequenceCD4-Positive T-LymphocytesCell LineCells, CulturedGene Products, envHIV-1HumansLentivirusMolecular Sequence DataMutationRNA, AntisenseSequence DeletionTransduction, GeneticVirus ReplicationGene Products, envRNA, Antisense

Identifiers

PMID15194784
PMCPMC421644
OpenAlexW2147475756

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.