Transcriptional Targeting Approaches in Cardiac Gene Transfer Using AAV Vectors

Cardiac-targeted transgene delivery offers new treatment opportunities for cardiovascular diseases, which massively contribute to global mortality. Restricted gene transfer to cardiac tissue might protect extracardiac organs from potential side-effects. This could be mediated by using cis-regulatory elements, including promoters and enhancers that act on the transcriptional level. Here, we discuss examples of tissue-specific promoters for targeted transcription in myocytes, cardiomyocytes, and chamber-specific cardiomyocytes. Some promotors are induced at pathological states, suggesting a potential use as induction-by-disease switches in gene therapy. Recent developments have resulted in the identification of novel enhancer-elements that could further pave the way for future refinement of transcriptional targeting, for example, into the cardiac conduction system.

Automated summary

Cardiac-targeted transgene delivery provides new treatment opportunities for cardiovascular diseases by using cis-regulatory elements to restrict gene transfer and protect extracardiac organs. Tissue-specific promoters for targeted transcription in specific cardiac cells have been identified, some of which are induced at pathological states and could potentially act as induction-by-disease switches in gene therapy.