Evidence map›Paper›PMID 20410930›Full record

ArticleGene therapy2010

Development of a nonintegrating Rev-dependent lentiviral vector carrying diphtheria toxin A chain and human TRAF6 to target HIV reservoirs.

Z Wang, Z Tang, Y Zheng, D Yu, M Spear, S R Iyer, B Bishop, Y Wu

Open access · bronzeAbstract read
In one paragraph

Article in Gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed, 27 citations in OpenAlex.

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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 1 institution in 2 countries.

Z WangTransplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, MA, USA.
Z Tang
Y Zheng
D Yu
M Spear
S R Iyer
B Bishop
Y Wu
George Mason University · US

Funding

Regulation of Cofilin in HIV-1 Infection of Human CD4 T CellsR01AI081568 · NIAID · GEORGE MASON UNIVERSITY · PI WU, YUNTAO · 2009 to 2012
$1.2M
Targeting Brain Macrophages by a novel lentiviral vectorR21NS051130 · NINDS · GEORGE MASON UNIVERSITY · PI WU, YUNTAO · 2005 to 2006
$358k
Determine the Transcriptional Activity of Non-integrated HIV-1 DNAR21AI069981 · NIAID · GEORGE MASON UNIVERSITY · PI WU, YUNTAO · 2007 to 2008
$340k
NIAID NIH HHS AI069981NIAID NIH HHS AI081568NIAID NIH HHS R01 AI081568NIAID NIH HHS R21 AI069981NINDS NIH HHS NS051130NINDS NIH HHS R21 NS051130
6 · The paper itself

Abstract

Persistence of human immunodeficiency virus (HIV) despite highly active antiretroviral therapy (HAART) is a lasting challenge to virus eradication. To develop a strategy complementary to HAART, we constructed a series of Rev-dependent lentiviral vectors carrying diphtheria toxin A chain (DT-A) and its attenuated mutants, as well as human tumor necrosis factor receptor-associated factor 6 (TRAF6). Expression of these suicide genes following delivery through viral particles is dependent on Rev, which exists only in infected cells. Among these toxins, DT-A has been known to trigger cell death with as little as a single molecule, whereas two of the attenuated mutants in this study, DT-A(176) and DT-A(Delta N), were well tolerated by cells at low levels. TRAF6 induced apoptosis only with persistent overexpression. Thus, these suicide genes, which induce cell death at different expression levels, offer a balance between efficacy and safety. To minimize possible mutagenesis introduced by retroviral integration in nontarget cells, we further developed a nonintegrating Rev-dependent (NIRD) lentiviral vector to deliver these genes. In addition, we constructed a DT-A-resistant human cell line by introducing a human elongation factor 2 mutant into HEK293T cells. This allowed us to manufacture the first high-titer NIRD lentiviral particles carrying DT-A to target HIV-positive cells.

Indexed as

ApoptosisCell DeathCell LineDiphtheria ToxinDNA, ViralFluoroimmunoassayGene Products, revGenetic TherapyGenetic VectorsHIV-1HIV InfectionsHumansLentivirusPeptide FragmentsTNF Receptor-Associated Factor 6Virus ReplicationDiphtheria Toxindiphtheria toxin fragment ADNA, ViralGene Products, revPeptide FragmentsTNF Receptor-Associated Factor 6

Identifiers

PMID20410930
PMCPMC2910233
OpenAlexW2083779362

What OpenQuestion holds

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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.