Messenger RNA (mRNA) therapeutics are attracting much attention, particularly after the approval of two mRNA vaccine formulations for COVID-19. However, as a therapeutic modality, mRNA still has issues of poor bioavailability, showing rapid enzymatic degradation in physiological environments and the tendency to induce uncontrollable inflammatory responses. Supramolecular approaches for mRNA delivery are a realistic strategy for improving its bioavailability, reducing immunogenicity and enhancing the translational activity. Among supramolecular mRNA formulations, polymeric micelles, i.e., core-shell nano-structures self-assembled by polyion complexation between catiomers and mRNA in aqueous conditions, can effectively reduce enzymatic degradation of mRNA in biological milieu through precise control of the polymer design. mRNA-loaded polymeric micelles can improve the intracellular delivery of mRNA toward safe and efficient mRNA delivery to various cells and organs. Moreover, polymeric micelles can be combined with orthogonal supramolecular approaches using complementary RNA oligonucleotides, which allows installing protective and functional moieties to mRNA, or crosslinking various mRNA strands, by engineered hybridization. Herein, I will present our recent efforts to apply polymer- and RNA-based supramolecular approaches for effectively transporting mRNA therapeutics to target cells in vivo.
Conférence proposée par Canal U, plus d’info sur le site de Canal U