National Grants
Grant of the Romanian National Authority for Scientific Research (CNCS – UEFISCDI)
Project PN-III-P1-1.1-PD-2016-1942 (Period: May 2, 2018 - March 31, 2020. Budget: 250.000 lei)
Project Title: Evaluation of the therapeutic potential of non-viral apolipoprotein E gene transfer to limit progression of atherosclerosis
Project team:
Dr. Trusca Georgeta Violeta, Project Director
Dr. Mariana Pinteala, Mentor
Project summary:
Apolipoprotein E (apoE) has lipid-lowering and anti-atherosclerotic effects, being involved in the clearance of cholesterol-rich lipoproteins and the cholesterol efflux from cells.
We hypothesize that an increase in apoE expression induced by fullerene-based nanosystems will confer anti-atherosclerotic protection and contribute to the regression of atherosclerotic plaques.
The goal of this project is to generate fullerene-based nanoparticles conjugated with DNA encoding full length or truncated forms of apoE under CMV promoter to be used for in vivo non-viral transfection as a therapeutic tool for limiting atherosclerosis progression.
The specific objectives are:
O1. To generate non-viral transfection agents for expression of apoE3 or its fragments.
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clone apoE3 or its fragments in a non-viral vector;
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couple the obtained plasmids to C60-PEI conjugates;
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test the functionality of C60-apoE/GFP polyplexes as non-viral transfection agents.
O2. To assess the timing and organs accumulation of apoE expression after in vivo transfection.
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determine the organs transfected by systemic delivery of C60-apoE/GFP polyplexes;
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test the time-course evolution of in vivo transfection with C60-apoE/GFP polyplexes.
O3. To evaluate the potential beneficial effects of apoE-polyplexes in experimental atherosclerosis using in vivo transfection.
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to evaluate the atherosclerotic plaque evolution after systemic delivery of apoE-polyplexes in apoE-deficient mice;
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to determine if the minimally invasive intramuscular injection of apoE-polyplexes is efficient in atherosclerotic plaque reduction in apoE-deficient mice.
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Schematic representation of project strategy |
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The results will reveal the therapeutic potential of non-viral apolipoprotein E gene transfer in atherosclerotic plaque regression, opening new horizons in the therapy of atherosclerosis.
Scientific Report (02/05/2018 — 20/12/2018)
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Scientific Report (December 2018 - December 2019)
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Scientific Report (December 2019 - Octomber 2020)