Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts.

Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Abstract Text:

C F McTiernan,M A Mathier,X Zhu,X Xiao,E Klein,C H Swan,H Mehdi,G Gibson,A M Trichel,J C Glorioso,A M Feldman,K R McCurry,B London,C F McTiernan,M A Mathier,X Zhu,X Xiao,E Klein,C H Swan,H Mehdi,G Gibson,A M Trichel,J C Glorioso,A M Feldman,K R McCurry,B London,

Sequestration of tumor necrosis factor-alpha (TNFalpha) by TNF-receptor immunoglobulin G (IgG)-Fc fusion proteins can limit heart failure progression in rodent models. In this study we directly injected an adeno-associated viruses (AAV)-2 construct encoding a human TNF receptor II IgG-Fc fusion protein (AAV-TNFRII-Fc) into healthy baboon hearts and assessed virally encoded gene expression and clinical response. Adult baboons received direct cardiac injections of AAV-TNFRII-Fc ( approximately 5 x 10(12) viral/genomes/baboon) or an equivalent dose of AAV-2 empty capsids, and were analyzed after 5 or 12 weeks. Viral genomes were restricted to the myocardium, and routine analyses (blood cell counts, clinical chemistries) remained unremarkable. Echocardiograms were unchanged but electrocardiograms revealed marked ST- and T-wave changes consistent with myocarditis only in baboons receiving AAV-TNFRII-Fc. TNFRII serum levels peaked at approximately 3 times the baseline levels at 1-2 weeks postinjection and subsequently declined to baseline levels. TNFRII-Fc protein and transcripts were detected in the heart at harvest. After AAV injection, anti-AAV-2 antibody levels increased in all baboons, while anti-TNFRII-Fc could not be detected. Baboons that received AAV-TNFRII-Fc developed myocardial infiltrates including CD8+ cells. Thus, a cellular immune response to cardiac delivery of AAV encoding foreign proteins may be an important consideration for AAV-based cardiac gene therapy.Gene Therapy (2007) 14, 1613-1622; doi:10.1038/sj.gt.3303020; published online 13 September 2007.

Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Publishing Authors By Initials

CF McTiernan,MA Mathier,X Zhu,X Xiao,E Klein,CH Swan,H Mehdi,G Gibson,AM Trichel,JC Glorioso,AM Feldman,KR McCurry,B London,CF McTiernan,MA Mathier,X Zhu,X Xiao,E Klein,CH Swan,H Mehdi,G Gibson,AM Trichel,JC Glorioso,AM Feldman,KR McCurry,B London,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Gene therapy

VOLUME: 14

Page Numbers: 1613-22

Journal Abbreviation: Gene Ther.

ISSN: 0969-7128

DAY: 13

MONTH: 09

YEAR: 2007

Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9421525

Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts.

AFFILIATION: 1Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA, USA.

Country: England

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Gene Ther

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor TNFRII-Fc in baboon hearts Related Publications

• A focused salivary gland infection with attenuated MCMV: an animal model with prevention of pathology associated with systemic MCMV infection.
• Acute pulmonary function response to ozone in young adults as a function of body mass index.
• Amiodarone and atrial fibrillation.
• Analyzing the structure of polypeptides in membranes by fluorescence quenching.
• Assessment of left ventricular global systolic function by transoesophageal echocardiography.
• Cerebral metabolism and mood in remitted opiate dependence.
• Comprehensive phenotypic analysis of the gut intra-epithelial lymphocyte compartment: perturbations induced by acute reovirus 1/L infection of the gastrointestinal tract.
• Corticolimbic dysregulation and chronic methamphetamine abuse.
• Determination of lysine pK values using [5-13C]lysine: application to the lyase domain of DNA Pol beta.
• Effect of ceramide N-acyl chain and polar headgroup structure on the properties of ordered lipid domains (lipid rafts).
• Effect of cigarette smoking on prefrontal cortical function in nondeprived smokers performing the Stroop Task.
• Effect of sequence hydrophobicity and bilayer width upon the minimum length required for the formation of transmembrane helices in membranes.
• Effect of the structure of lipids favoring disordered domain formation on the stability of cholesterol-containing ordered domains (lipid rafts): identification of multiple raft-stabilization mechanisms.
• Effects of cigarette smoking and abstinence on stroop task performance.
• Frontoparietal cortical activity of methamphetamine-dependent and comparison subjects performing a delay discounting task.
• GSTM1 and GSTP1 and respiratory health in asthmatic children exposed to ozone.
• Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy.
• Genetic variation in S-nitrosoglutathione reductase (GSNOR) and childhood asthma.
• Knockin animal models of inherited arrhythmogenic diseases: what have we learned from them?
• Mouse models of long QT syndrome.
• Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts.
• NMR analysis of [methyl-13C]methionine UvrB from Bacillus caldotenax reveals UvrB-domain 4 heterodimer formation in solution.
• Patient education: teaching patients about wound care.
• Perioperative Beta blockades: facts and controversies.
• The control of transmembrane helix transverse position in membranes by hydrophilic residues.
• The phenyltetraene lysophospholipid analog PTE-ET-18-OMe as a fluorescent anisotropy probe of liquid ordered membrane domains (lipid rafts) and ceramide-rich membrane domains.
• The role of small molecule inhibitors for veterinary patients.
• The role of the neurobiologist in redefining the diagnosis of autism.
• Traffic exposure and lung function in adults: the Atherosclerosis Risk in Communities study.
• Working memory in cigarette smokers: comparison to non-smokers and effects of abstinence.