Eventos

Reprogramming the Factory of Life to Target the Delivery of mRNA via Helical Chirality

Virgil Percec, Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia

Homochiral helical self-organizations are known at the macroscopic level in nature, art, architecture and science for thousands of years [1a,b]. However, molecular helicity was discovered in proteins and DNA [2] only in the early 1950^th and in molecular, macromolecular and supramolecular complex nanosystems emerged soon after [1c,d,e,f]. Our ability to program functions at the supramolecular level based on helical chirality is less advanced than the same process at the macroscopic level during Archimedes and Leonardo da Vinci times. The principles “discover-elucidate mechanism-predict programmed primary structure” elaborated in our laboratory and aided by synthetic methodologies developed also in our laboratory for accelerated modular-orthogonal synthesis of programmed structures such us Ni-catalyzed cross-coupling, mixed-ligand, thio-bromo click, SET-organic and polymerizarion reactions, self-accelerated and self-interrupted synthesis including selected examples of homochiral helical self-organizations and functions together with the molecular factory of life will be briefly explained. The origins of helical homochirality is equivalent to the origins of life although the origins and the rational of biological membranes homochirality continues to be debated [3]. Inspiration from amphiphilic Janus dendrimers [4a] and Janus glycodendrimers [4b] discovered in our laboratory allowed to transit from the commercial viral and four-component lipid nanoparticle synthetic vectors for delivery of mRNA to the one-component ionizable multifunctional sequence-defined amphiphilic Janus dendrimers (IAJDs) delivery vector [5]. The current status of the molecular design principles providing the least expensive and the simplest access to targeted delivery of mRNA with programmed IAJDs will be discussed in great details. Targeted delivery of mRNA to all organs is expected to change the field of nanomedicine at the most fundamental level by providing unprecedented avenues to new vaccines and therapeutics.