Event
BIOE Seminar Series: Peixuan Guo (The Ohio State University)
Friday, September 18, 2020
9:00 a.m.-10:00 a.m.
Virtual
Xiaoming (Shawn) He
shawnhe@umd.edu
Join us for the Bioengineering Seminar Series, which connects experts from around the country with our faculty, students, and staff to discuss their recent findings. Everyone is welcome!
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Dr. Peixuan Guo
Sylvan G. Frank Endowed Chair, Pharmaceutics and Pharmacology
School of Pharmacy
The Ohio State University
RNA as a stretchable negative polymer and Lego block to build controllable 3D and 4D nanostructures for material and biomedical applications
Happiness is a personal feeling. The happiness of a hard-working scientist is the exploration of the unknown word that can resulted in self-rewarding and self-comfort. As earlier as 1987, I found that besides the mRNA, tRNA, rRNA and ribozyme that have been already known at that time, cells had many small RNA (sRNA) molecules with novel functions yet undiscovered and I called them “sRNA” (Guo et al. A small viral RNA is required for in vitro packaging of bacteriophage phi29 DNA. Science 1987; 236:690). In 1998, I proved the concept of RNA nanotechnology (Guo et al, Mol Cell, 1998, featured in Cell; 4 papers in Nature Nanotech 2010, 2011, 2018). We proved that RNA nanoparticles can be used for cancer therapy (Guo lab in Human Gene Therapy, 2005, Nano Letters 2005, Gene Therapy 2006). In 2014, I predicted that a third milestone in the history of pharmaceutical drug development will be RNA as drugs or drugs that dock to (Shu, et al, and Guo, Adv Drug Delivery Reviews, 2014; 2014; 66:74). The recent approval of several RNA based drugs by the FDA demonstrates that the third milestone is coming.
RNA nanotechnology is the construction of nano-architectures by bottom-up self-assembly with a scaffold, ligands, therapeutics, and regulators, comprised mainly or exclusively of RNA. A variety of programmable stable RNA nanoparticles with defined shape, size, and stoichiometry have been developed for diverse applications. RNA nanoparticles can self-assemble into a homogeneous structure with defined stoichiometry. These nanoparticles with 2’- modifications are thermodynamically and chemically stable, non-toxic, and highly soluble; display favorable biodistribution and PK/PD profiles; and retain authentic folding and independent functionalities of all incorporated modules (ie. RNA aptamer, siRNA, miRNA or ribozyme). During the last several years, the three major challenges became resolved concerning RNase degradation, in vivo dissociation, and immune responses. The rising popularity of RNA nanotechnology is mainly due to the following achievements: (1) introducing chemical modifications into nucleotides without significantly altering the RNA folding or self-assembly; (2) confirming the concept that RNA structures have very high thermodynamic stability and is suitable for in vivo circulation and other applications; (3) developing methods to control shape, size, and stoichiometry of RNA nanoparticles; (4) proving that the immunogenicity of RNA nanoparticles is size, shape, structure and sequence dependent and is tunable to produce either a minimal immune response that can serve as safe therapeutic vectors, or a strong immune response for cancer immunotherapy or vaccine adjuvants; (5) decreasing cost of RNA production by chemical synthesis; (6) demonstrating the production of safe and specific targeting therapeutic RNA nanoparticles for cancer and other diseases with little or no accumulation in vital organs.
About the Speaker
Dr. Peixuan Guo is the first to prove the concept of RNA nanotechnology, has held three Endowed Chair Professor positions at three prestigious universities including the College of Pharmacy at the University of Kentucky; and the College of Pharmacy at The Ohio State University (OSU)., and a Distinguished Faculty Scholar of Purdue. Currently he is Sylvan G. Frank Endowed Chair Professor in Pharmaceutics and Drug Delivery; the director of the Center of RNA Nanobiotech and Nanomedicine at OSU; the president of the International Society of RNA Nanotechnology and Nanomedicine (ISRNN). He is also the Chairman of the Board of Directors for ExonanoRNA LLC, and Foshan Weina Biomedicine Inc both focusing on the development of RNA therapeutics for cancers using the RNA Nanotechnology he invented and leads internationally. He received his Ph.D. in Microbiology and Genetics from University of Minnesota, then postdoctoral training at NIH under Bernard Moss, a member of the National Academy of Science. He was an Assistant Professor of molecular virology at Purdue in 1990, tenured in 1993, became full Professor in 1997 and was honored as a Purdue Distinguished Faculty Scholar in 1998. He was the Director of NIH Nanomedicine Development Center from 2006-2011 and the director of NCI Cancer Nanotechnology Platform Partnership Program on RNA Nanotechnology for Cancer Therapy from 2012-2017. As earlier as 1987 he envisioned that cells have many small RNA molecules with novel functions undiscovered, and named them “sRNA” (Guo et al. A small viral RNA is required for in vitro packaging of bacteriophage phi29 DNA. Science 1987; 236:690). He also constructed the first viral DNA packaging motor (PNAS 1986); first one to reported that viral DNA packaging is driven by ATPase, and identified the protein sequence for ATP binding (JBC 1986) that is the same sequence motif that 8 years later James Walker received his Novel Price in 1995; determined that one ATP is used to package two bp of dsDNA (JBC 1986); revealed pRNA hexamer (Mol Cell 1998) that has led to the emergence of the field of RNA Nanotech; pioneered RNA nanotechnology (Mol Cell 1998, featured in Cell; and 4 papers in Nature Nanotech 2010,2011,2018); developed a TIRF Photobleaching dual imaging System to count single-fluorophores (EMBOJ 2007); incorporated phi29 motor channel into membrane (Nature Nanotech 2009) for single pore sensing and RNA and peptide sequencing (licensed to Oxford Nanopore); discovered a third class of biomotor using revolution mechanism; developed approaches for ultra-potent drug development. He was honored for Pfizer Distinguished Faculty Award; Purdue Faculty Scholar Award; Lions Club Cancer Res Award; Distinguished Alumni of U of Minnesota; 100 Years Distinguished Chinese Alumni of U of Minnesota. He has been editor or on the editorial board of 7 nanotech journals including the Executive Deputy Editor of Molecular Therapy/Nucleic Acids and the co-founder of Nanomedicine BMN. He was reported numerous times by TV or media such as ABC, NBC, ACS; featured by NIH, NSF, MSNBC, NCI and ScienceNow as well as by NIH director Francis Collins’ office. He has been the organizer or founding chair of 8 international conferences and GRC conferences on RNA Nanotechnology; and was previously a member of two prominent national nanotech initiatives by NSF, NIH, National Council of Nanotechnology and NIST, as well as the member of two NIH steering committees in nanotechnology.
