Conventional pacemakers have a finite battery life and hence need replacements which involves cost and discomfort of the surgical procedure. Genetically engineered pacemakers could be a possible alternative to implantable electronic devices for the treatment of bradyarrhythmias. The strategies for a biological pacemaker include: upregulation of beta receptors, conversion of myocytes into pacemaker cells and stem cell therapy. The unresolved issues are the longevity and safety of pacemaker genes. Potential for induction of arrhythmias have also to be considered.

Stem cell and somatic reprogramming methods have been applied to develop putative pacemaker cells from non pacemaker cells. Recent discoveries in the molecular biology of sinus node has triggered research in this direction. Minimally invasive somatic reprogramming has been done in pigs with complete heart block. Adenoviral TBX18 gene transfer was used and pacemaker activity was detected from the intramyocardial injection site from day two and persisted throughout the duration of the two week study period, with minimal back up electronic pacemaker use.

Transforming working myocardium into surrogate sinoatrial node by gene transfer is still further down in the translational pipeline. A review of the topic in 2020 mentioned that till then, a biological pacemaker had been successfully applied in big mammals, but it is still a long way from clinical uses for treatment of human heart diseases. They also proposed potential research directions for generating a biological pacemaker based on cardiac computational modelling.

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