A brief discussion of the discovery of the field-effect transistor (FET) and its impact on our daily life will be followed by the history of the discoveries and of the development of the 4-component and 1-component delivery systems for nucleoside-modified messenger RNA (mRNA)[1,2]. The four-component systems contain phospholipids, PEG-conjugated lipids, cholesterol and an ionizable amine co-assemble with mRNA into lipid nanoparticles (LNPs)[3] which are difficult to assemble and have not known distribution of their components. The 1-component multifunctional sequence-defined ionizable Janus dendrimer (IAJD)[4] delivery synthetic vectors inspired from amphiphilic Janus dendrimers (JDs),[5a] amphiphilic Janus glycodendrimers (JGDs),[5b] and sequence-defined JGDs[5c] require fewer synthetic steps than any of each of the 4-component LNPs, and co-assemble with mRNA into dendrimersome nanoparticles (DNPs)[4] by a simple injection process[4,5]. Their DNPs have precise placement of their functional groups. The advantages and disadvantages of 4-and 1-components systems, together with their current state of the art will be presented. Targeted delivery to all organs is expected to provide vaccines and therapeutics for infectious diseases, cancers, heart and degenerative diseases to name just a few. The simple and inexpensive 1-component IAJDs are expected to generate access to nanomedicine in both developed and underdeveloped countries. A comparison with the impact of the transistor in the 20th century will conclude this lecture. 

Acknowledgments: Financial support from the National Science Foundation grants DMR-2104554, DMR-1720530, P.Roy Vagelos Chair at the University of Pennsylvania. 

References:
[1] Kariko, K.; Buckstein, M. ; Ni, H.; Weissman, D. Immunity 2005, 23, 166. 
[2] Pardi, N.; Hogan, J.M.; Porter, F.W.; Weissman, D. Nature Rev. Drug. Discov. 2018, 17, 261. 
[3] Cullis, P.L. Lab Angew. Chem. Int. Ed. 2012, 51, 8529.