Evidence map›Paper›PMID 25420215›Full record

ArticleHuman gene therapy2015

Gene delivery of a viral anti-inflammatory protein to combat ocular inflammation.

Cristhian J Ildefonso, Henrique Jaime, Masmudur M Rahman, Qiuhong Li, Shannon E Boye, William W Hauswirth, Alexandra R Lucas, Grant McFadden, Alfred S Lewin

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 29% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Meta-Analysis on the Association of ALDH2 Polymorphisms and Type 2 Diabetic Mellitus, Diabetic Retinopathy.International journal of environmental research and public health · 2017
    Pooled it
  2. Review
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  14. A Drug-Tunable Gene Therapy for Broad-Spectrum Protection against Retinal Degeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Article
  15. Article
  16. Diabetic retinopathy: Breaking the barrier.Pathophysiology : the official journal of the International Society for Pathophysiology · 2017
    Review
  17. 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

9 authors at 1 institution in 1 country.

Cristhian J Ildefonso1 Department of Molecular Genetics and Microbiology, University of Florida College of Medicine , Gainesville, FL 32610.
Henrique Jaime
Masmudur M Rahman
Qiuhong Li
Shannon E Boye
William W Hauswirth
Alexandra R Lucas
Grant McFadden
Alfred S Lewin
University of Florida · US

Funding

rAAV-CNGB3 Gene Therapy for Achromatopsia: Translational Research StudiesR24EY022023 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2013 to 2017
$7.9M
Engineering AAV for safe and efficient gene delivery to the human retinaR01EY024280 · NEI · UNIVERSITY OF FLORIDA · PI Shannon Elizabeth Boye · 2014 to 2026
$7.5M
Vision Research CoreP30EY021721 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2011 to 2015
$2.8M
Manipulation of inflammasomes and NF-kB signaling in human myeloid cells by MyxomR01AI100987 · NIAID · UNIVERSITY OF FLORIDA · PI MCFADDEN, GRANT · 2013 to 2017
$1.9M
NEI NIH HHS P30 EY02172NEI NIH HHS P30 EY021721NEI NIH HHS R01 EY02025NEI NIH HHS R01 EY024280NEI NIH HHS R24 EY022023NIAID NIH HHS R01 AI100987
6 · The paper itself

Abstract

Inflammation of the retina is a contributing factor in ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration (AMD). The M013 immunomodulatory protein from myxoma virus has been shown to interfere with the proinflammatory signaling pathways involving both the NLRP3 inflammasome and NF-κB. We have developed and characterized an adeno-associated viral (AAV) vector that delivers a secretable and cell-penetrating form of the M013 protein (TatM013). The expressed TatM013 protein was secreted and blocked the endotoxin-induced secretion of interleukin (IL)-1β in monocyte-derived cells and the reactive aldehyde-induced secretion of IL-1β in retinal pigment epithelium cells. The local anti-inflammatory effects of AAV-delivered TatM013 were evaluated in an endotoxin-induced uveitis (EIU) mouse model after intravitreal injection of mice with an AAV2-based vector carrying either TatM013 fused to a secreted green fluorescent protein (GFP) tag (sGFP-TatM013) or GFP. Expression of the sGFP-TatM013 transgene was demonstrated by fluorescence funduscopy in living mice. In EIU, the number of infiltrating cells and the concentration of IL-1β in the vitreous body were significantly lower in the eyes injected with AAV-sGFP-TatM013 compared with the eyes injected with control AAV-GFP. These results suggest that a virus-derived inhibitor of the innate immune response, when delivered via AAV, could be a generalized therapy for various inflammatory diseases of the eye.

Indexed as

Gene Transfer TechniquesRecombinant Fusion ProteinsAnimalsCell Line, TumorCell-Penetrating PeptidesDependovirusDisease Models, AnimalGene ExpressionGene OrderGene Products, tatGenes, ReporterGenetic TherapyGenetic VectorsHumansInterleukin-1betaMiceCell-Penetrating PeptidesGene Products, tatInterleukin-1betaRecombinant Fusion Proteinstat Gene Products, Human Immunodeficiency VirusViral Proteins

Identifiers

PMID25420215
PMCPMC4303190
OpenAlexW2045525369

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.