Myocardial Gene Transfer: Routes and Devices for Regulation of Transgene Expression by Modulation of Cellular Permeability

Katz, Michael G.; Fargnoli, Anthony S.; Bridges, Charles R.

doi:10.1089/hum.2012.241

Cited by 14 publications

(21 citation statements)

References 112 publications

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“…Electroporation (EP) either affects the passive transport of a plasmid in close proximity to the cell surface or allows DNA to be internalized when the electric field is applied because DNA actively binds to the cell membrane [13]. DNA binding to the cell membrane may be possible due to direct interaction with the cells [14], and uptake into the cell membrane may be facilitated due to the DNA's negative charge [15].…”

Section: Physical Transfectionmentioning

confidence: 99%

“…These include but are not limited to problems with the contrast agents and equipment used, such as concentration and preparation of contrast agents, pulse and exposure duration, acoustic pressure and transducer frequency [15].…”

Section: Ultrasound-based Transfection (Sonoporation)mentioning

confidence: 99%

“…The small holes then facilitate the uptake of exogenous DNA into the cell membrane. The permeability of the membrane at the laser site is mediated by local temperature changes [15]. The effects of laser-based transfection are not affected by receptors or interactions within the cell membrane, rather they appear to be dependent upon the differences in osmotic pressure between the cytoplasm and the extracellular matrix [8].…”

Section: Laser-based Transfectionmentioning

confidence: 99%

“…Subsequently, DNA is taken up into the cell and released into the cytoplasm [25]. The applied MF has been shown to cause changes in venular permeability with extravasation [26], but the actual uptake of vectors into the cell seems to depend on the increased or decreased permeability of the cell membrane after the application of the MF [15,26,27].…”

Section: Magnetic Field-based Transfection (Magnetofection)mentioning

confidence: 99%

“…One study showed that certain magnetic nanobead-polymer-DNA complexes had a 36-to 85-fold greater transfection efficiency compared with controls in vitro, while an analogous in vivo model using an epicardial magnet transferred the same complexes to the heart. This resulted in both strong reporter and therapeutic gene expression [15].…”

Section: Magnetic Field-based Transfection (Magnetofection)mentioning

confidence: 99%

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Methods to improve cardiac gene therapy expression

Scimia

Sydnes

Zuppo

et al. 2014

Expert Review of Cardiovascular Therapy

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Gene therapy strategies are becoming a valuable approach for the treatment of heart failure. Some trials are ongoing and others are being organized. Vascular access in clinical experimentation is still the chosen modality of delivery, but many other approaches are in research and development. A successful gene therapy strategy involves not only the choice of the right vector and gene, but also the correct delivery strategy that allows for transduction of the highest percentage of cardiomyocytes, limited spilling of virus into other organs and the possibility to correlate the amount of injected virus to the rate of the expression within the cardiac tissue. The authors will first concentrate on clarifying what the barriers are that the virus has to overcome in order to reach the nuclei of the target organs and methodologies that have been tested to improve the range of expression.

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Section: Physical Transfectionmentioning

confidence: 99%

Section: Ultrasound-based Transfection (Sonoporation)mentioning

confidence: 99%

Section: Laser-based Transfectionmentioning

confidence: 99%

Section: Magnetic Field-based Transfection (Magnetofection)mentioning

confidence: 99%

Section: Magnetic Field-based Transfection (Magnetofection)mentioning

confidence: 99%

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Methods to improve cardiac gene therapy expression

Scimia

Sydnes

Zuppo

et al. 2014

Expert Review of Cardiovascular Therapy

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A Needleless Liquid Jet Injection Delivery Approach for Cardiac Gene Therapy

Fargnoli¹,

Katz²,

Bridges³

2016

Methods in Molecular Biology

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Fundamentally, cardiac gene therapy clinical trials have demonstrated that route efficiency is paramount in achieving maximum myocardial expression within safety limits. Gene transfer phenomena are largely influenced by physical transport principles (i.e., pressure, residence time, dispersion trafficking, mechanical resistance) that are independent of therapeutic characteristics. An alternative to intracoronary infusion methods, in an effort to improve efficiency in terms of cardiac specificity, is direct myocardial delivery via surgical injection. Direct injection methods circumvent the blood's immunological components and the cardiac system's native anatomical barriers by directly administering product into the myocardium. In addition, this approach offers the advantage of precise site selection. Two unresolved problems with direct delivery wherein the novel needleless liquid jet approach may resolve are: (1) initial therapeutic retention and (2) subsequent host responses associated with highly focal expression.In this protocol, we present a novel approach to improve direct cardiac gene delivery using a needleless liquid jet methodology. The liquid jet application is essentially a device concept that accelerates and disperses the therapeutic at a targeted myocardial site. The core hypothesis offered is that this approach, with optimized settings, could result in increased therapeutic retention in the initial delivery phase. This would theoretically result in more total myocardial expression per dose while at the same time providing a more homogenous profile around the injection site. Therefore, this would increase efficiency in terms of transduced muscle per delivery site and offer a significant improvement to standard intramuscular injection.

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Molecular Cardiac Surgery with Recirculating Delivery (MCARD): Procedure and Vector Transfer

Katz

Fargnoli

Kendle³

et al. 2016

Methods in Molecular Biology

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Despite progress in clinical treatment, cardiovascular diseases are still the leading cause of morbidity and mortality worldwide. Therefore, novel therapeutic approaches are needed, targeting the underlying molecular mechanisms of disease with improved outcomes for patients. Gene therapy is one of the most promising fields for the development of new treatments for the advanced stages of cardiovascular diseases. The establishment of clinically relevant methods of gene transfer remains one of the principal limitations on the effectiveness of gene therapy. Recently, there have been significant advances in direct and transvascular gene delivery methods. The ideal gene transfer method should be explored in clinically relevant large animal models of heart disease to evaluate the roles of specific molecular pathways in disease pathogenesis. Characteristics of the optimal technique for gene delivery include low morbidity, an increased myocardial transcapillary gradient, esxtended vector residence time in the myocytes, and the exclusion of residual vector from the systemic circulation after delivery to minimize collateral expression and immune response. Here we describe myocardial gene transfer techniques with molecular cardiac surgery with recirculating delivery in a large animal model of post ischemic heart failure.

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Myocardial Gene Transfer: Routes and Devices for Regulation of Transgene Expression by Modulation of Cellular Permeability

Cited by 14 publications

References 112 publications

Methods to improve cardiac gene therapy expression

Methods to improve cardiac gene therapy expression

A Needleless Liquid Jet Injection Delivery Approach for Cardiac Gene Therapy

Molecular Cardiac Surgery with Recirculating Delivery (MCARD): Procedure and Vector Transfer

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