Evidence map›Paper›PMID 10364297›Full record

ArticleJournal of virology1999

Amelioration of retroviral vector silencing in locus control region beta-globin-transgenic mice and transduced F9 embryonic cells.

C S Osborne, P Pasceri, R Singal, T Sukonnik, G D Ginder, J Ellis

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 55 citations in OpenAlex.

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  12. Stable gammaretroviral vector expression during embryonic stem cell-derived in vitro hematopoietic development.Molecular therapy : the journal of the American Society of Gene Therapy · 2006
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  18. Rhesus monkey placental transgene expression after lentiviral gene transfer into preimplantation embryos.Proceedings of the National Academy of Sciences of the United States of America · 2001
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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 3 institutions in 2 countries.

C S OsbornePrograms in Developmental Biology and Blood and Cancer Research, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
P Pasceri
R Singal
T Sukonnik
G D Ginder
J Ellis
Hospital for Sick Children · CAUniversity of Minnesota Medical Center · USVirginia Commonwealth University · US

Funding

GLOBIN GENE REGULATION DURING ERYTHROID DIFFERENTIATIONR37DK029902 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI GINDER, GORDON D · 1992 to 1999
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NIDDK NIH HHS R37 DK029902NIDDK NIH HHS R37-DK29902
6 · The paper itself

Abstract

Retroviral vectors are transcriptionally silenced in hematopoietic stem cells, and this phenomenon must be overcome for effective gene therapy of blood diseases. The murine stem cell virus (MSCV) vector completely silences beta-globin reporter genes regulated by locus control region (LCR) elements 5'HS2 to 5'HS4 in seven of eight transgenic mice. Here, we show that no single known MSCV silencer element is sufficient for complete LCR beta-globin transgene silencing. However, partial silencing of high-copy transgenes is conveyed by the MSCV direct repeat and promoter elements. The CpG methylation pattern of silenced and expressed MSCV promoter transgenes is virtually identical, demonstrating that silencing does not absolutely correlate with methylation status. Combined mutations in all four MSCV silencer elements leads to expression of beta-globin in 6 of 10 transgenic mice. The same mutations incorporated into the HSC1 retrovirus vector direct neo gene expression in 71% of transduced F9 embryonic carcinoma cells. These studies demonstrate that combined mutation of four retroviral silencer elements relieves complete silencing in most transgenic mice and transduced F9 cells and suggests that novel silencer elements remain. Enhanced expression of the HSC1 vector in primitive stem cells is well suited for blood gene therapy applications.

Indexed as

Gene Expression Regulation, ViralGenetic VectorsLocus Control Region3T3 CellsAnimalsDNA MethylationGenes, ReporterGlobinsMiceMice, TransgenicMoloney murine leukemia virusMutagenesisTerminal Repeat SequencesTumor Cells, CulturedGlobins

Identifiers

PMID10364297
PMCPMC112606
OpenAlexW2114538338

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.