Evidence map›Paper›PMID 11313827›Full record

ArticleGene therapy2001

Influence of multiplicity of infection and protein stability on retroviral vector-mediated gene expression in hematopoietic cells.

A Wahlers, M Schwieger, Z Li, D Meier-Tackmann, C Lindemann, H G Eckert, D von Laer, C Baum

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In one paragraph

Article in Gene therapy, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

27 citing papers in PubMed, 74 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 2 institutions in 1 country.

A WahlersDepartment Cell and Virus Genetics, Heinrich-Pette-Institute, Hamburg, Germany.
M Schwieger
Z Li
D Meier-Tackmann
C Lindemann
H G Eckert
D von Laer
C Baum
Leibniz Institute of Virology (LIV) · DEUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Using retroviral vectors encoding enhanced green fluorescent protein (EGFP), we addressed to what extent expression of retroviral transgenes in hematopoietic cells depends on the multiplicity of infection (MOI) and on the half-life of the encoded protein. We show that an elevation of the MOI not only elevates the frequency of transduced cells, but also increases transgene expression levels and reduces interanimal variability in vivo (hematopoietic cells of C57BL/6J mice analyzed 13 weeks after transplantation). This suggests that the MOI has to be carefully controlled and should be adapted as desired for clinical studies when evaluating vector performance in preclinical models. The impact of protein stability is demonstrated by comparing vectors expressing EGFP or a destabilized variant with a C-terminal PEST-sequence, d2EGFP. The loss of expression with d2EGFP was more pronounced in terminally differentiated cells of the peripheral blood (>30 fold) than in progenitor cells (five- to 10-fold), indicating a stronger transcription of the retroviral promoter in progenitor cells and a predominant role of protein inheritance over de novo synthesis of transgenic protein in mature blood cells. This analysis reveals an important and differentiation-dependent contribution of protein half-life to the expression of retroviral vectors in hematopoietic cells, establishes d2EGFP as a more accurate reporter for determination of vector transcription, and also suggests that preclinical data obtained under conditions of high transduction rates or with vectors expressing stable reporter proteins require careful interpretation.

Indexed as

Transcription, GeneticAnimalsAntigens, CD34Bone Marrow CellsGene ExpressionGenetic TherapyGenetic VectorsGreen Fluorescent ProteinsHalf-LifeHematopoietic Stem CellsHumansLuminescent ProteinsMiceMice, Inbred C57BLRetroviridaeTime FactorsAntigens, CD34Green Fluorescent ProteinsLuminescent Proteins

Identifiers

PMID11313827
OpenAlexW2314777822

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.