IBEC Seminar: Virgil Percec

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.

References

1. (a) Percec, V.; Xiao, Q. Bull. Chem. Soc. Jpn. 2021, 94, 900-928. (b) Percec, V.; Adamson, J.; Gianti, E. Supramolecular Nanotechnology, Wiley-VCH, 2023, Azzaroni, O.; Conda-Sheridan, M. Eds. Vol.1, p. 1-123. (c) Percec, V. Lab. Science 1997, 278, 449-452. (d) Nature 1998, 391,161-164. (e) Nature 2002, 419, 384-387. (f) Nature 2004, 430, 764-768.
2. (a) Pauling, L.; Corey, J. Am. Chem. Soc. 1950, 72, 5349-5349; (b) Watson, J. D.; Crick, F.H.C. Nature 1953, 171, 737-738; (c) Percec, V.; Xiao, Q. CHEM 2021, 7, 529-536; (d) Percec, V. CHEM 2023, August issue.
3. Percec, V. Lab. J. Am. Chem. Soc. 2023, 145, 4311-4323.
4. (a) Percec, V. Lab. Science, 2010, 328, 1009-1014; (b) Percec, V. Lab. J. Am. Chem. Soc. 2013, 135, 9055-9077.
5. (a) Percec, V. and Weissman D. Labs. J. Am. Chem. Soc. 2021, 143, 12315-12325; (b) J. Am. Chem. Soc. 2021, 143, 18803-12325; (c) J. Am. Chem. Soc. 2022, 144, 4746-4753; (d) Pharmaceutics 2023, 15, 1572; (e) J. Am. Chem. Soc. Submitted.

Virgil Percec was born and educated in Romania (BS in Organic and Macromolecular Chemistry at the Polytechnic University in Iasi, PhD in 1976 with C. I. Simionescu. In 1981 he defected his native country and after short postdoctoral stays at the University of Freiburg in Germany (July 1981 with H. -J. Cantow) and University of Akron, US (August 1981 to March 1982 with J. P. Kennedy) he joined the Department of Macromolecular Science of Case Western Reserve University in Cleveland, US in March 1982 as an Assistant Professor. He was promoted to Associate Professor in 1984 and to Professor in 1986. In 1993 he was awarded the Leonard Case Jr. Chair at Case Western Reserve University and in 1999 he was invited and moved to the University of Pennsylvania in Philadelphia as P. Roy Vagelos Chair and Professor of Chemistry. He has been repeatedly a Visiting Professor at the Universities of Freiburg, Ulm and at the Max Planck Institute for Polymer Research in Mainz (all in Germany) and at the Royal Institute of Technology in Stockholm. His research interest is at the interface between organic, supramolecular, macromolecular chemistries, liquid crystals, nanoscience and biology where he contributed over 820 refereed publications, 80 patents, edited 20 books and presented over 1300 endowed, invited and plenary lectures. He educated over 3509 students and postdocs over 70 of them being in university professors all over the world.

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