Evidence map›Paper›PMID 19741733›Full record

ArticleGene therapy2010

Foamy combinatorial anti-HIV vectors with MGMTP140K potently inhibit HIV-1 and SHIV replication and mediate selection in vivo.

H-P Kiem, R A Wu, G Sun, D von Laer, J J Rossi, G D Trobridge

Abstract readEvaluation Study
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 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

45 citing papers in PubMed, 65 citations in OpenAlex.

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  13. Insulated Foamy Viral Vectors.Human gene therapy · 2016
    Article
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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

6 authors at 5 institutions in 2 countries.

H-P KiemClinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109-1024, USA. hkiem@fhcrc.org
R A Wu
G Sun
D von Laer
J J Rossi
G D Trobridge
University of Washington · USBeckman Research InstituteCity of Hope · USFred Hutch Cancer Center · USGeorg Speyer Haus · DE

Funding

CORE--VECTOR PRODUCTIONP30DK056465 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERNSTEIN, IRWIN D · 1999 to 2014
$14.9M
COMBINATORIAL USE OF CCR5 RIBOZYMES WITH ANTI HIV1 RNASR01AI042552 · NIAID · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI ROSSI, JOHN JOSEPH · 1998 to 2019
$7.8M
Suplement to Safety and Efficacy of AIDS Gene Therapy in MonkeysP01AI061839 · NIAID · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI ROSSI, JOHN JOSEPH · 2004 to 2007
$7.1M
Development of Novel AIDS Gene Therapy Strategies in the Macaque SHIV ModelR01AI080326 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KIEM, HANS-PETER · 2009 to 2012
$2.2M
Efficacy and Safety of Foamy Retroviral Vectors for AIDS Gene TherapyR21AI063959 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TROBRIDGE, GRANT D · 2006 to 2007
$511k
Stem Cell Gene Therapy for Pyruvate Kinase Deficiency Using Foamy VectorsR21DK077806 · NIDDK · WASHINGTON STATE UNIVERSITY · PI TROBRIDGE, GRANT D · 2008 to 2009
$466k
NIAID NIH HHS AI061839NIAID NIH HHS AI063959NIAID NIH HHS AI42552NIAID NIH HHS P01 AI061839NIAID NIH HHS R01 AI042552NIAID NIH HHS R01 AI080326NIAID NIH HHS R21 AI063959NIDDK NIH HHS DK077806NIDDK NIH HHS DK56465NIDDK NIH HHS P30 DK056465NIDDK NIH HHS R21 DK077806
6 · The paper itself

Abstract

Highly active antiretroviral therapy has greatly reduced the morbidity and mortality from human immunodeficiency virus (HIV) infection, but AIDS continues to be a serious health problem worldwide. Despite enormous efforts to develop a vaccine, there is still no cure, and alternative approaches including gene therapy should be explored. In this study we developed and compared combinatorial foamy virus (FV) anti-HIV vectors that also express a mutant methylguanine methyltransferase (MGMTP140K) transgene to increase the percentage of gene-modified cells after transplantation. These FV vectors inhibit replication of HIV-1 and also the simian immunodeficiency virus/HIV-1 (SHIV) chimera that can be used in monkey AIDS gene therapy studies. We identified a combinatorial FV vector that expresses 3 anti-HIV transgenes and inhibits viral replication by over 4 logs in a viral challenge assay. This FV anti-HIV vector expresses an HIV fusion inhibitor and two short hairpin RNAs (shRNAs) targeted to HIV-1 tat and rev, and can be produced at high titer (3.8 x 10(7) transducing units ml(-1)) using improved helper plasmids suitable for clinical use. Using a competitive repopulation assay, we show that human CD34(+) cells transduced with this combinatorial FV vector efficiently engraft in a mouse xenotransplantation model, and that the percentage of transduced repopulating cells can be increased after transplantation.

Indexed as

Genetic VectorsHIV-1Simian Immunodeficiency VirusAnimalsDNA Modification MethylasesDNA Repair EnzymesGenetic TherapyGene Transfer TechniquesHematopoietic Stem Cell TransplantationHumansMiceSimian foamy virusTransduction, GeneticTransgenesTumor Suppressor ProteinsVirus ReplicationDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanTumor Suppressor Proteins

Identifiers

PMID19741733
PMCPMC3162371
OpenAlexW2084630935

What OpenQuestion holds

Textmetadata
LicenceTDM
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.