The Use of Gene Therapy for Ablation of Atrial Fibrillation

Abstract

Atrial fibrillation is the most common clinically significant cardiac arrhythmia, increasing the risk of stroke, heart failure and morbidity and mortality. Current therapies, including rate control and rhythm control by antiarrhythmic drugs or ablation therapy, are moderately effective but far from optimal. Gene therapy has the potential to become an attractive alternative to currently available therapies for atrial fibrillation. Various gene transfer vectors have been developed for cardiovascular disease with viral vectors being most widely used due to their high efficiency. Several gene delivery methods have been employed on different therapeutic targets. With increasing understanding of arrhythmia mechanisms, novel therapeutic targets have been discovered. This review will evaluate state-of-art gene therapy strategies and approaches including sinus rhythm restoration and ventricular rate control that could eventually prevent or eliminate atrial fibrillation in patients.

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

“…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 .…”

“…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.…”

Therapeutic Prospects of Gene Therapy for Atrial Fibrillation

“…It has been used in cardiac applications. However, its main shortcomings include a very low transfection efficiency in vivo and only transient gene expression, limiting its application [22,23]. The most widely used viral vector in cardiac gene therapy experiments is the adenoviral vector.…”

“…It is able to transduce the mammalian heart with a very high efficiency and provides a great way to undertake proof-of-principle studies. This vector's main limitation is its ability to induce a rapid inflammatory and immune response resulting in a limited expression window of about two weeks [23]. Lentiviral vectors on the other hand are capable of long-term gene expression by virtue of their ability to integrate into the host cell genome.…”

“…Furthermore, the absence of sufficient dedicated atrial vasculature limits intracoronary perfusion delivery methods [31]. The two related methods that have been shown to be effective for delivering vectors to the atrium, epicardial painting and direct epicardial injection, entail a mini-thoracotomy for access [20,23,30]. Epicardial painting was the first method used for vector delivery to the atrium [32].…”