Disease-relevant cardiac mRNA

Disease-relevant cardiac mRNA refers to a broad class of messenger RNA molecules that are either targeted for therapeutic inhibition or utilized as therapeutic agents to treat cardiovascular conditions. This category includes endogenous mRNAs that are overexpressed or mutated in disease states—such as the transthyretin (TTR) mRNA in amyloid cardiomyopathy or phospholamban (PLN) in heart failure—which can be silenced using antisense oligonucleotides (ASOs) or small interfering RNA (siRNA) (Front. Bioeng. Biotechnol., 2022). Additionally, it encompasses synthetic, modified mRNAs (modRNAs) designed to encode therapeutic proteins directly within the myocardium, such as VEGF-A to promote angiogenesis or Relaxin to improve cardiac output (Portland Press, 2023). The most advanced clinical application of this technology is AZD8601, a modRNA encoding VEGF-A that has been investigated for its ability to improve heart function following myocardial infarction (European Heart Journal, 2023). Despite its potential, the use of cardiac mRNA faces significant hurdles, including the requirement for efficient, heart-specific delivery systems like lipid nanoparticles (LNPs) and the need to minimize immunogenic responses to exogenous nucleic acids (IntechOpen, 2022).

Other names

Cardiac mRNAHeart-specific mRNATherapeutic cardiac mRNACardiac modified mRNACardiac modRNA

Drugs targeting or utilizing disease-relevant cardiac mRNA operate through two main modalities: mRNA-based protein replacement, where synthetic modified mRNA (modRNA) is delivered to the heart to express therapeutic proteins (e.g., VEGF-A for angiogenesis), and mRNA silencing, where antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) bind to and trigger the degradation of pathogenic endogenous mRNAs (e.g., TTR mRNA in amyloidosis).