Michael Mellas, Ph.D.

Michael is working to develop a polyelectrolyte complex micelle system composed of cationic polypeptides and RNA, to deliver miRNA to inflamed vascular endothelial cells to induce RNA interference (RNAi) to inhibit plaque development. RNAi has been shown to efficaciously control gene expression, but developing this promising mode of therapy requires overcoming challenges such as evading the body’s defenses, targeting the cells to be treated, and entering those cells. The polyelectrolyte complexes provide both a shield for the miRNA and a scaffold on which to attach a targeting moiety. The bottom-up assembly of amphiphile micelles readily allows for modular multifunctional assemblies that can actively target cells and trigger a therapeutic effect simultaneously. By employing vascular cell adhesion molecule 1 (VCAM-1) as the targeting agent, Michael aims to achieve active targeting of inflamed endothelial cells, to inhibit development of plaques while avoiding off-target effects. He is currently exploring the modularity of the system, varying the targeting peptide or miRNA inside to change the target cell or effect, respectively. He is also working to increase the repertoire of nucleic acids to include longer nucleic acids such as mRNA or DNA, which will expand the potential mechanisms through which this system could induce therapeutic effects.