Intramyocardial gene transfer of vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart

Ojalvo, Ariana G.; Seralena, Alina; Vispo, Nelson Santiago; Silva, Ricardo; González, Nemecio; Guevara, Luis; Batista, Juan F.; Montequin, J Fernandez; Chaos, Nicolas; González, Rafael Lazcano; Reima, Camilo; Peña, Yamilé; Coca, Marcos; Perera, Alejandro; Vázquez, Roberto; Puchades, Yaquelín; Garcia-Osuna, Tamara; Dominguez, Heberto; Reyes, José Luis; Ali, Alfonso; Herrera, L.

doi:10.2225/vol7-issue3-fulltext-12

Cited by 2 publications

(2 citation statements)

References 25 publications

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“…As a number of clinical trials have been conducted in the area, the trial type is also specified. Naked plasmid VEGF-A121 Preclinical Ojalvo [112] Naked plasmid VEGF-A165 Clinical Ripa [113] Naked plasmid VEGF-A165 Preclinical Son [114] Naked plasmid VEGF-A165 Clinical Gyongyosi [115] Naked plasmid VEGF-A165 Preclinical Yoon [116] Naked plasmid VEGF-A165 Clinical Kastrup [117] Naked plasmid VEGF-A165 Preclinical Radke [118] Naked plasmid VEGF-A165 Preclinical Sarkar [119] Naked plasmid VEGF-A165 Preclinical Kloner [120] Naked plasmid VEGF-A165 Preclinical Schwarz [121] Naked plasmid VEGF-A165 Clinical Losordo [122] Naked plasmid VEGF-A165 Preclinical Rutanen [86] Naked plasmid VEGF-A165 and GSF (granulocyte stimulating factor) Clinical Wang [123] Naked plasmid VEGF-C Clinical Vale [85] …”

Section: Other Factors and Peptidesmentioning

confidence: 99%

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Non‐viral gene therapy for myocardial engineering

Holladay

O’Brien

Pandit

2010

WIREs Nanomed Nanobiotechnol

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Despite significant advances in surgical and pharmacological techniques, myocardial infarction remains the main cause of morbidity in the developed world because no remedy has been found for the regeneration of infarcted myocardium. Once the blood supply to the area in question is interrupted, the inflammatory cascade, among other mechanisms, results in the damaged tissue becoming a scar. The goals of cardiac gene therapy are essentially to minimize damage, to promote regeneration or some combination thereof. While the vector is, in theory, less important than the gene being delivered, the choice of vector can have a significant impact. Viral therapies can have very high transfection efficiencies, but disadvantages include immunogenicity, retroviralmediated insertional mutagenesis and the expense and difficulty of manufacture. For these reasons, researchers have focused on non-viral gene therapy as an alternative. In this review, naked plasmid delivery, or the delivery of complexed plasmids, and cellmediated gene delivery to the myocardium will be reviewed. Pre-clinical and clinical trials in the cardiac tissue will form the core of the discussion. While unmodified stem cells are sometimes considered therapeutic vectors based on paracrine mechanisms of action basic understanding is limited. Thus, only genetically modified cells will be discussed as cell-mediated gene therapy.Ischemic heart disease, which includes acute damage due to myocardial infarction (MI) and chronic damage due to atherosclerotic narrowing of vessels, accounts for 35% of deaths reported in the United States every year [1]. MI, which is literally the death of cardiac tissue due to lack of 2 oxygen supply, is the result of the occlusion of a coronary artery. Within a few hours of interrupted blood supply, affected cardiomyocytes die. While the body has adaptive mechanisms, such as hypertrophy of the undamaged cardiac muscle and the development of collateral blood supply to minimize the damage, ischemic heart disease remains the most common cause of death in developed countries [2].The delivery of plasmid DNA to the myocardium is a complicated problem as the transfection efficiency of unmodified DNA is quite low, but complexation with agents designed to improve transfection can increase the cytotoxicity of the treatment [3]. Delivery of uncomplexed plasmid DNA is conceptually the simplest gene delivery technique, but these plasmids have extremely low transfection efficiencies in vitro and are not particularly effective in vivo. Compared to viral vectors, transgene expression is almost negligible and the expression time is also very limited [4]. However, there are significant advantages in using plasmids instead of viruses, such as ease of preparation (large and small scale), very low immunogenicity (as there are essentially no protein or membrane components in the plasmid), capacity for long term storage, ease of recombinant manipulation and much larger expression cassettes [4]. A variety of non-viral techniques are available to improve...

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Section: Other Factors and Peptidesmentioning

confidence: 99%

“…Furthermore, if the MI has been induced by coronary artery ligation, the heart is already exposed. This technique has definite advantages, as a physician can directly observe the beating heart and select areas in need of treatment [112,122,125].…”

Section: Thoracotomymentioning

confidence: 99%

Non‐viral gene therapy for myocardial engineering

Holladay

O’Brien

Pandit

2010

WIREs Nanomed Nanobiotechnol

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Indirect and competitive enzyme-linked immunosorbent assays for monitoring the humoral response against human VEGF

Ramírez

Díaz

Lasa

et al. 2016

Journal of Immunoassay and Immunochemistry

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CIGB-247, a VEGF-based vaccine, was studied in a clinical trial. This advance demands the refinement of the methodologies for assessment of vaccine immune responses. This study aimed to improve the performance of ELISAs for detecting IgG antibodies against human VEGF and the blocking activity of the serum to inhibit the VEGF/VEGFR2 interaction. The best experimental conditions were established through the evaluation of several blocking buffers, immobilization surfaces, and plate suppliers using human sera as test samples. As a result, two controlled ELISAs were used in testing of elicited immune response against VEGF in patients immunized with CIGB-247.

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Intramyocardial gene transfer of vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart

Cited by 2 publications

References 25 publications

Non‐viral gene therapy for myocardial engineering

Non‐viral gene therapy for myocardial engineering

Indirect and competitive enzyme-linked immunosorbent assays for monitoring the humoral response against human VEGF

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