Strategies to deliver microRNAs as potential therapeutics in the treatment of cardiovascular pathology

Chistiakov, Dimitry A.; Sobenin, Igor A.; Orekhov, Alexander N.

doi:10.3109/10717544.2012.738436

Cited by 38 publications

(35 citation statements)

References 128 publications

(93 reference statements)

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“…Clinical success of these methods however depends on effective delivery of LNA-reagents into affected target tissues. Pharmacological stability, tissue penetration, transport across cell membranes, escaping from nucleases and finally specific neutralization of target miR are some of the issues currently being investigated (68–70). Recent advances in the development of nanocarriers and functionalized nanopartlcles have helped in improving microRNA-mediated targeted therapies.…”

Section: Hypoxia Inducible Factor (Hif)mentioning

confidence: 99%

Vascular Endothelial Growth Factor Signaling in Hypoxia and Inflammation

Ramakrishnan

Anand

Roy

2014

J Neuroimmune Pharmacol

285

220

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Infection, cancer and cardiovascular diseases are the major causes for morbidity and mortality in the United States according to the Center for Disease Control. The underlying etiology that contributes to the severity of these diseases is either hypoxia induced inflammation or inflammation resulting in hypoxia. Therefore, molecular mechanisms that regulate hypoxia-induced adaptive responses in cells are important areas of investigation. Oxygen availability is sensed by molecular switches which regulate synthesis and secretion of growth factors and inflammatory mediators. As a consequence, tissue microenvironment is altered by reprogramming metabolic pathways, angiogenesis, vascular permeability, pH homeostasis to facilitate tissue remodeling. Hypoxia inducible factor (HIF) is the central mediator of hypoxic response. HIF regulates several hundred genes and vascular endothelial growth factor (VEGF) is one of the primary target genes. Understanding the regulation of HIF and its influence on inflammatory response offers unique opportunities for drug development to modulate inflammation and ischemia in pathological conditions.

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Section: Hypoxia Inducible Factor (Hif)mentioning

confidence: 99%

Vascular Endothelial Growth Factor Signaling in Hypoxia and Inflammation

Ramakrishnan

Anand

Roy

2014

J Neuroimmune Pharmacol

285

220

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“…More effective targeting and delivery methods for rosiglitazone would simultaneously improve efficacy and specificity. Other promising strategies for treating cardiovascular disease include stem cells for repair of ischemic myometrium and valve damage [12]; macromolecular-assisted, thiomer-mediated approaches [13]; nanoparticle-assisted therapies [14,15] and microRNA-mediated gene expression modulation therapy [16]. This review will focus on strategies and mechanisms of ultrasound (US)-mediated cardiovascular drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-mediated drug delivery for cardiovascular disease

Sutton

Haworth

Pyne‐Geithman

et al. 2013

Expert Opinion on Drug Delivery

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Introduction Ultrasound (US) has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. These effects can be mediated by mechanical oscillations of circulating microbubbles, or US contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi or direct drugs to optimal locations for delivery. Areas covered The present review summarizes investigations that have provided evidence for US-mediated drug delivery as a potent method to deliver therapeutics to diseased tissue for cardiovascular treatment. In particular, the focus will be on investigations of specific aspects relating to US-mediated drug delivery, such as delivery vehicles, drug transport routes, biochemical mechanisms and molecular targeting strategies. Expert opinion These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery and new US technologies. Successful implementation of US-mediated drug delivery has the potential to change the way many drugs are administered systemically, resulting in more effective and economical therapeutics, and less-invasive treatments.

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“…In particular, DNA de-methylation agents 5-azacytidine and zebularine were reported to be capable of trans-differentiation enhancement [70], while histone deacetylase inhibitor valproic acid was used to potentiate de-differentiation [71]. In addition, cell fate reprogramming was shown to be augmented by miRNAs [72]. Clearly, miRNAs can be delivered in conjunction with mRNA.…”

Section: Where Do Mrna-based Vectors Stay Among Other Gene Vectors Fomentioning

confidence: 99%

“…Clearly, miRNAs can be delivered in conjunction with mRNA. It is expected that robotic systems for combinatorial screening can be used to search for suitable reprogramming mixtures of mRNA vectors, protein factors, miRNAs and small molecular weight molecules [72].…”

Section: Where Do Mrna-based Vectors Stay Among Other Gene Vectors Fomentioning

confidence: 99%

Design and Production of mRNA-based Gene Vectors for Therapeutic Reprogramming of Cell Fate

Tolmachov¹

2014

Gene Technology

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Recent advances in therapeutically important cell fate reprogramming fuelled a renaissance in the use of mRNAbased gene vectors. Thus, mRNA vectors were successfully employed to induce lasting epigenetic changes in various target cells making them short-listed vector candidates for the manufacture of therapeutic engraftment materials for autologous transplantation, artificial human tissues for drug discovery via high-throughput screening projects and also for therapeutic cell trans-differentiation directly in the human body. De-differentiation of cells into 'induced pluripotent stem cells', transgene-directed differentiation and trans-differentiation require the simultaneous delivery of a number of regulatory factors, and, favourably, potent reprogramming vector cocktails can be straightforwardly assembled from a selection of mRNA species. In addition, several proteins can be conveniently expressed from a single mRNA using internal ribosome entry sites (IRESes) or, alternatively, fusion proteins supplemented with 'polypeptide-cleaving' ribosome skipping sequences. This review is focused on the design and production of cell-fate changing mRNAs.

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Strategies to deliver microRNAs as potential therapeutics in the treatment of cardiovascular pathology

Cited by 38 publications

References 128 publications

Vascular Endothelial Growth Factor Signaling in Hypoxia and Inflammation

Vascular Endothelial Growth Factor Signaling in Hypoxia and Inflammation

Ultrasound-mediated drug delivery for cardiovascular disease

Design and Production of mRNA-based Gene Vectors for Therapeutic Reprogramming of Cell Fate

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