Cardiac-targeted transgene delivery using tissue-specific promoters and novel enhancer-elements offers potential for refining transcriptional targeting in gene therapy for cardiovascular diseases.
Transcriptional targeting using specific promoters and enhancers offers a promising strategy to restrict AAV-mediated gene expression to the heart, minimizing off-target effects.
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.
Schröder et al. (Mon,) conducted a review in Cardiovascular diseases. Cardiac-targeted transgene delivery using AAV vectors was evaluated. Cardiac-targeted transgene delivery using tissue-specific promoters and novel enhancer-elements offers potential for refining transcriptional targeting in gene therapy for cardiovascular diseases.