Keywords: heart disease, microRNA, nanotherapy, DNA nanotechnology

 

Cardiovascular diseases are the main cause of death globally. Nearly 50% of these deaths are due to ischaemic heart disease, including myocardial infarction.  Myocardial infarction can lead to myocardial remodelling that can progress to heart failure.

 

Despite this, there is no specific therapy for myocardial regeneration after myocardial infarction to prevent the maladaptive remodelling and progress towards heart failure ^[1]. Therefore, the objective of our study is the development of a novel nanotherapy capable of inducing myocardial regeneration leveraging forefront DNA nanotechnology.

 

MiR-199a-3p has shown to induce cardiac regeneration through its pro-proliferative action on cardiomyocytes in studies carried out in infarcted mice, rats and pigs ^[2,3,4]. We have generated DNA nanostructures (DNS) built by the self-assembly of DNA strandswhose sequence is adequately designed to load large amounts of miR-199a-3p through Watson-Crick-Franklin base-pairing interactions. DNS have been characterized by gel electrophoresis (GE), dynamic light scattering and atomic force microscopy. In vitro release of the loaded miR produced by RNAse H has been investigated by GE. Also, we have created a functional assay based on luciferase reporter activity and miR sponges to measure the activity of the miR intracellularly. This proves the interaction of the miR-199a-3p with its target gene sequence once released from the DNS by the intracellular RNAse H. In conclusion, our results show the formation of a DNS capable of carrying and releasing a therapeutic miR intracellularly and its functionality in vitro on its target sequence.