Evidence map›Paper›PMID 10505100›Full record

ArticleGene therapy1999

Prevention of autoimmune diabetes by intramuscular gene therapy with a nonviral vector encoding an interferon-gamma receptor/IgG1 fusion protein.

G J Prud'homme, Y Chang

Abstract read
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In one paragraph

Article in Gene therapy, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed, 78 citations in OpenAlex.

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  13. Prevention of type 1 diabetes by gene therapy.The Journal of clinical investigation · 2004
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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

2 authors at 1 institution in 1 country.

G J Prud'hommeDepartment of Pathology, McGill University, Montreal, Qc, Canada.
Y Chang
McGill University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We report on long-term delivery of an interferon-gamma (IFN gamma) inhibitory protein by intramuscular (i.m.) gene therapy. IFN gamma is a cytokine that plays an important role in many inflammatory disorders, including autoimmune insulin-dependent diabetes mellitus (IDDM) in NOD mice and (in various strains) multiple low-dose streptozotocin (STZ)-induced diabetes (MDSD). By cDNA insertion into plasmid VICAL VR-1255 we constructed an expression vector encoding a soluble IFN gamma receptor/IgG1 heavy chain (all murine) fusion protein (IFN gamma R/IgG1). This protein is secreted as a homodimer and neutralizes IFN gamma in vitro. We show that i.m. injections of this vector as naked DNA in mice results in secretion of IFN gamma R/IgG1, with serum levels exceeding 100 ng/ml for months after treatment. These levels are sufficient to neutralize IFN gamma in vivo, and to prevent either MDSD or cyclophosphamide (CYP)-accelerated diabetes in NOD mice, which are both characterized by systemic release of IFN gamma. In these diseases gene therapy considerably reduces inflammation in the islets of Langerhans (insulitis). Also, circulating IFN gamma R/IgG1 blocked IFN gamma-enhanced nitric oxide production by peritoneal macrophages. The fusion protein is constructed from non-immunogenic self elements, avoiding a neutralizing immune response and making it suitable for prolonged therapy of numerous inflammatory disorders.

Indexed as

AnimalsCell LineDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1FemaleGenetic TherapyGenetic VectorsImmunoglobulin GImmunoglobulin Heavy ChainsInjections, IntramuscularInterferon-gammaIslets of LangerhansMacrophage ActivationMiceMice, Inbred NODPlasmidsImmunoglobulin GImmunoglobulin Heavy ChainsInterferon-gammaReceptors, InterferonRecombinant Fusion Proteins

Identifiers

PMID10505100
OpenAlexW2334059217

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.