Background and Aims: ApoA-1 containing HDL lipoproteins are the major cholesterol acceptors from extra-hepatic tissues. In normal condition, their role in reverse cholesterol transport (RCT) favours lipid homeostasis. Furthermore, they are one of the key effectors in atheroprotection when dyslipidemia occurs and accordingly they have been widely studied1. Nowadays, in vitro reconstituted-HDL (rHDL) can be adequately produced and applied in biomedicine research. Referred to the cardiovascular field, it has been demonstrated that treatments based on rHDL are beneficial both in vitro and in animal studies. However, despite promising, rHDL infusions have failed to reach the prespecified efficacy endpoints when mortality benefit has been tested in clinical trials2. Therefore, with the aim to overcome this handicap, we have set up a methodology to “functionalize” rHDL with a microRNA in order to improve their therapeutic outcomes.