Discussion

Over the past two decades a host of new molecular pathways have been uncovered that guide mammalian heart development and disease. The ability to genetically manipulate these pathways in vivo have largely been dependent on the generation of genetically engineered mouse model systems or the transfer of exogenous genes in a variety of DNA vectors (plasmid, adenoviral, adeno-associated viruses, anti-sense oligonucleotides, etc.). Recently, a new approach to manipulate the gene program of the adult mammalian heart has been reported that will quickly allow the high efficiency expression of virtually any protein in the intact heart of mouse, rat, porcine, non-human primate, and human heart cells via the generation of chemically modified mRNA (modRNA). The technology platform has important implications for delineating the specific paracrine cues that drive human cardiogenesis, and the pathways that might trigger heart regeneration via the rapid generation of modRNA libraries of paracrine factors for direct in vivo administration. In addition, the strategy can be extended to a variety of other cardiovascular tissues, and solid organs across multiple species, and recent improvements in the core technology have supported moving the first in human studies of modRNA in the next two years. These recent advances are reviewed along with examples of the utility of the approach into quickly delineating novel insights into new therapeutics for regenerative cardiology as well as projections of the potential impact of the technology for a host of other biomedical problems in the cardiovascular system.