Therapeutic Prospects of Gene Therapy for Atrial Fibrillation

Farraha, Melad; Chong, James J.H.; Kizana, Eddy

doi:10.1016/j.hlc.2016.04.011

Cited by 12 publications

(10 citation statements)

References 42 publications

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“…Because sarcolipin expression is increased in heart failure states (Figure ), the sarcolipin promoter in diseased states may be advantageous, similar to that of the ANF promoter . Furthermore, current therapeutic gene transfer for atrial fibrillation is highly limited, such as direct injection to the right and left atrium or to the atrioventricular node for rate control . However, these approaches can lead to tissue damage and inflammatory response .…”

Section: Discussionmentioning

confidence: 99%

“…11 Furthermore, current therapeutic gene transfer for atrial fibrillation is highly limited, such as direct injection to the right and left atrium or to the atrioventricular node for rate control. 31,32 However, these approaches can lead to tissue damage and inflammatory response. 33,34 The most effective reported method is the gene painting method, which uses a poloxamer gel, dilute trypsin and vector mixture to increase contact time and penetration.…”

Section: Fluorescence Imagingmentioning

confidence: 99%

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Enhancing atrial‐specific gene expression using a calsequestrin cis‐regulatory module 4 with a sarcolipin promoter

Yoo

Kohlbrenner

Kim

et al. 2018

The Journal of Gene Medicine

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Background Cardiac gene therapy using the adeno‐associated virus serotype 9 vector is widely used because of its efficient transduction. However, the promoters used to drive expression often cause off‐target localization. To overcome this, studies have applied cardiac‐specific promoters, although expression is debilitated compared to that of ubiquitous promoters. To address these issues in the context of atrial‐specific gene expression, an enhancer calsequestrin cis‐ regulatory module 4 ( CRM4 ) and the highly atrial‐specific promoter sarcolipin were combined to enhance expression and minimize off tissue expression. Methods To observe expression and bio‐distribution, constructs were generated using two different reporter genes: luciferase and enhanced green fluorescent protein (EGFP). The ubiquitous cytomegalovirus (CMV), sarcolipin (SLN) and CRM4 combined with sarcolipin ( CRM4 .SLN) were compared and analyzed using the luciferase assay, western blotting, a quantitative polymerase chain reaction and fluorescence imaging. Results The CMV promoter containing vectors showed the strongest expression in vitro and in vivo . However, the module SLN combination showed enhanced atrial expression and a minimized off‐target effect even when compared with the individual SLN promoter. Conclusions For gene therapy involving atrial gene transfer, the CRM4 .SLN combination is a promising alternative to the use of the CMV promoter. CRM4 .SLN had significant atrial expression and minimized extra‐atrial expression.

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Section: Discussionmentioning

confidence: 99%

Section: Fluorescence Imagingmentioning

confidence: 99%

Enhancing atrial‐specific gene expression using a calsequestrin cis‐regulatory module 4 with a sarcolipin promoter

Yoo

Kohlbrenner

Kim

et al. 2018

The Journal of Gene Medicine

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“…With recent improvements in gene transfer vectors, delivery methods, and viable options for clinical translation, several inroads have been developed for gene therapy treatment of AF. 60 Gene therapy for AF rate control Most cases of AF are associated with an elevated ventricular rate. Because the AV node is the only conduction pathway between the atrium and ventricles, strategies are directed at increasing the refractoriness of the AV node to reduce the ventricular rate.…”

Section: Atrial Fibrillationmentioning

confidence: 99%

Gene and Cell Therapy for Cardiac Arrhythmias

Ravindran

Kok

Farraha

et al. 2020

Clinical Therapeutics

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Purpose: In the last decade, interest in gene therapy as a therapeutic technology has increased, largely driven by an exciting yet modest number of successful applications for monogenic diseases. Setbacks in the use of gene therapy for cardiac disease have motivated efforts to develop vectors with enhanced tropism for the heart and more efficient delivery methods. Although monogenic diseases are the logical target, cardiac arrhythmias represent a group of conditions amenable to gene therapy because of focal targets (biological pacemakers, nodal conduction, or stem cellerelated arrhythmias) or bystander effects on cells not directly transduced because of electrical coupling.Methods: This review provides a contemporary narrative of the field of gene therapy for experimental cardiac arrhythmias, including those associated with stem cell transplant. Recent articles published in the English language and available through the PubMed database and other prominent literature are discussed.Findings: The promise of gene therapy has been realized for a handful of monogenic diseases and is actively being pursued for cardiac applications in preclinical models. With improved vectors, it is likely that cardiac disease will also benefit from this technology. Cardiac arrhythmias, whether inherited or acquired, are a group of conditions with a potentially lower threshold for phenotypic correction and as such hold unique potential as targets for cardiac gene therapy.Implications: There has been a proliferation of research on the potential of gene therapy for cardiac arrhythmias. This body of investigation forms a strong basis on which further developments, particularly with viral vectors, are likely to help this technology progress along its translational trajectory.

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“…1,8,9 One can, therefore, consider that the future of gene editing for the treatment and prevention of human diseases is still quite uncertain. Few studies have sought to anticipate future possibilities related to the use of gene editing technologies for the treatment and prevention of human diseases, [14][15][16][17] and none explored the different possibilities of application of the various programmable nucleases (meganuclease, ZFN, TALEN, LEAPER, and CRISPR) for the treatment and prevention of various types of human diseases (cancer, infectious diseases, and hereditary monogenic and polygenic diseases). Our study addresses this gap by assessing the views of gene editing-related researchers from all over the world, who took part in a web-based survey.…”

Section: Introductionmentioning

confidence: 99%

Gene Editing for Treatment and Prevention of Human Diseases: A Global Survey of Gene Editing-Related Researchers

2020

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In the next decades, gene editing technologies are expected to be used in the treatment and prevention of human diseases. Yet, the future uses of gene editing in medicine are still unknown, including its applicability and effectiveness to the treatment and prevention of infectious diseases, cancer, and monogenic and polygenic hereditary diseases. This study aims to address this gap by analyzing the views of over 1,000 gene editing-related researchers from all over the world. Some of our survey results show that, in the next 10 years, DNA double-strand breaks are expected to be the main method for gene editing, and CRISPR-Cas systems to be the mainstream programmable nuclease. In the same period, gene editing is expected to have more applicability and effectiveness to treat and prevent infectious diseases and cancer. Off-targeting mutations, reaching therapeutic levels of editing efficiency, difficulties in targeting specific tissues in vivo, and regulatory and ethical challenges are among the most relevant factors that might hamper the use of gene editing in humans. In conclusion, our results suggest that gene editing might become a reality to the treatment and prevention of a variety of human diseases in the coming 10 years. If the future confirms these researchers' expectations, gene editing could change the way medicine, health systems, and public health deal with the treatment and prevention of human diseases.

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Therapeutic Prospects of Gene Therapy for Atrial Fibrillation

Cited by 12 publications

References 42 publications

Enhancing atrial‐specific gene expression using a calsequestrin cis‐regulatory module 4 with a sarcolipin promoter

Enhancing atrial‐specific gene expression using a calsequestrin cis‐regulatory module 4 with a sarcolipin promoter

Gene and Cell Therapy for Cardiac Arrhythmias

Gene Editing for Treatment and Prevention of Human Diseases: A Global Survey of Gene Editing-Related Researchers

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