Genome Editing and Atrial Fibrillation

Inherited arrhythmias and gene therapy: Are there any ethical considerations to take into account?

“…Because gene variability is widespread in channelopathies, additional genetic variants are being found and included in the prospective catalog of variations amenable to genetic analysis[ 1 , 11 ]. Even though both patient-dependent and patient-independent in vitro techniques could corroborate a variant’s pathogenic potential, more compelling data and statistical validation of disorder etiology are required before they could be included in commonly utilized medical testing[ 1 - 4 ]. Furthermore, despite significant advances in comprehending the pathophysiology of familial rhythm disturbances, guidelines for treatment approaches, such as beta-blockers, left cardiac sympathetic denervation, or implantable cardioverter-defibrillator, have not altered in the previous 40 years[ 1 - 4 ].…”

“…Even though both patient-dependent and patient-independent in vitro techniques could corroborate a variant’s pathogenic potential, more compelling data and statistical validation of disorder etiology are required before they could be included in commonly utilized medical testing[ 1 - 4 ]. Furthermore, despite significant advances in comprehending the pathophysiology of familial rhythm disturbances, guidelines for treatment approaches, such as beta-blockers, left cardiac sympathetic denervation, or implantable cardioverter-defibrillator, have not altered in the previous 40 years[ 1 - 4 ]. The ability to incorporate unique disease-causing variants while maintaining the same genetic origin allows for an impartial assessment of different mutations[ 1 - 4 ].…”

“…Furthermore, despite significant advances in comprehending the pathophysiology of familial rhythm disturbances, guidelines for treatment approaches, such as beta-blockers, left cardiac sympathetic denervation, or implantable cardioverter-defibrillator, have not altered in the previous 40 years[ 1 - 4 ]. The ability to incorporate unique disease-causing variants while maintaining the same genetic origin allows for an impartial assessment of different mutations[ 1 - 4 ]. This comparison research revealed that various variants in the same gene could be the result of unique genetic pathways, strengthening the viewpoint that the therapy of familial rhythm disturbances must shift toward targeted therapy and patient-specific treatments[ 2 , 12 ].…”

“…While often effective in relieving or preventing symptoms, current pharmacological or interventional treatments do not specifically address the underlying genetic defect or the key intermediary pathways implicated in the development of these disorders[ 3 ]. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques, in particular, have the ability to modify the genetic electrophysiologic substrate, hence enabling treatment for many lethal disorders[ 4 ]. So far, gene therapy has enabled the in vitro replication of rhythm disturbances, offering a consistent framework for variable pathogenesis, pathophysiological, and drug-testing research[ 1 - 4 ].…”

“…Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques, in particular, have the ability to modify the genetic electrophysiologic substrate, hence enabling treatment for many lethal disorders[ 4 ]. So far, gene therapy has enabled the in vitro replication of rhythm disturbances, offering a consistent framework for variable pathogenesis, pathophysiological, and drug-testing research[ 1 - 4 ]. Nevertheless, in vivo procedures still require further investigation into the techniques’ reliability, precision, and efficacy.…”