Draft:Peixuan Guo

Peixuan Guo
郭培宣
File:Headshot of Peixuan.jpg Headshot of Peixuan Guo
Born	April 4, 1951 China
Alma mater	University of Minnesota
Scientific career
Fields	Virology, RNA Nanotechnology, Nanopore Technology
Institutions	Purdue University, University of Cincinnati, University of Kentucky, Ohio State University
Doctoral advisor	Enzo Paoletti and Bernard Moss
Website	https://rnanano.osu.edu/Guo/peixuanguo.html

Peixuan Guo

Peixuan Guo (born April 4, 1951) is a Chinese-American virologist and nanotechnologist. He is the Sylvan G. Frank Endowed Chair in Pharmaceutics and Drug Delivery and the director of the Center for RNA Nanobiotechnology and Nanomedicine at The Ohio State University. He is also a Fellow of the National Academy of Inventors.

Guo is known for proposing the idea that a large number of previously undiscovered small RNA exist in cells called sRNA (Guo P et al. A small viral RNA is required for in vitro packaging of bacteriophage phi29 DNA. Science 1987; 236: 690); constructed 1st viral DNA packaging motor (PNAS 1986); discovered phi29 motor pRNA (Science, 1987); proved the concept of RNA nanotechnology (Mol Cell 1998, featured in Cell,1998; 4 papers in Nat Nanotechnol 2009, 2010, 2011, 2018; Nature Comm, 2019); he invented a novel method for the production of the vaccinia virus mRNA capping enzyme (PNAS, 1990 ,7:4023) that are used currently as an essential component for the production of COVID-19 mRNA vaccine; his team invented a patented method for the production of COVID-19 mRNA vaccine, invented a method for the use of TIRF System to count single-fluorophores molecules (EMBOJ, 2007); invented a unique method for single pore sensing by incorporating phi29 motor channel into the membrane (Nat Nanotechnol, 2009); discovered a 3rd class of biomotor using revolving mechanism without rotation; discovered that RNA is like rubber and amoeba with unusually high efficiency for passive tumor targeting and regression with quick kidney clearance, thus undetectable toxicity. He invented the methods to use RNA nanotechnology to make the insoluble and toxic cancer drugs soluble and nontoxic and invented RNA nanotechnology to decorate exosomes with a ligand for cancer targeting using the directionality of antibody-like (i.e., Y-shaped) RNA arrowtail (Nat Nanotechnol, 2017). He also invented method for the delivery of RNAi to the cytosol of cancer cells without endosome trapping; his team invented Exojuice for exosome purification with a simple one step 2  by combination of zonal and density gradient. All these invention has enable his team to achieve the treatment of liver cancer, lung cancer, brain cancer, colorectal cancer, breast cancer; stomach cancer, and prostate cancer in preclinical trials. ExonanoRNA LLC, whom Guo is the founder of, is actively working toward clinical trials for the treatment of these cancers. 

Guo has 70 Patents filed, 16 patents granted, and 54 are in provisional and PCT; most of them are in RNA nanotechnology and therapeutics, and RNA-ligand displayed exosomes for the delivery of RNAi.

Early life and education

Guo was born April 4, 1951 in China. He received his PhD from the University of Minnesota in 1987. He was a postdoctoral associate at the New York State Department of Health where he worked with Professor Enzo Paoletti on molecular virology. He was also a postdoctoral scientist for the NIH - Institute of Infectious Diseases where he worked with Professor Bernard Moss, who is a member of the National Academy of Sciences. Guo became a professor at Purdue University in 1990.

Awards and honors

• 1995 - Pfizer Distinguished Faculty Award for Research Excellence
• 1999 - Purdue Faculty Scholar
• 2000 - Purdue Faculty Scholar
• 2001 - Purdue Faculty Scholar
• 2002 - Purdue Faculty Scholar
• 2003 - Purdue Faculty Scholar
• 2004 - Purdue Faculty Scholar
• 2005 - One of five finalists for Feynman (Nobel Prize Laureate) Nanotechnology Award
• 2006 - Lions Club Award for Cancer Research Excellence
• 2009 - Distinguished Alumni of the University of Minnesota
• 2010 - Distinguished Research Award, University of Cincinnati
• 2011 - Distinguished Research Award, University of Cincinnati
• 2014 - Distinguished Chinese Alumni of the 100 years of University of Minnesota
• 2021 - Named “Innovator of the Year” of the Ohio State University
• 2022 - Fellow of the National Academy of Inventors

Inventions and Discoveries

1. His team has invented a method to completely inhibit the lung cancer metastasis (Patent filed in Feb 2023, manuscripts in preparation)

2. Early on, Dr. Guo discovered and proposed the idea that many small RNA molecules exist in cells with novel function yet remained undiscovered, and he named them sRNA (Guo P et al. A small viral RNA is required for in vitro packaging of bacteriophage phi29 DNA. Science, 1987; 236: 690). Today, many small RNA molecules including miRNA, piRNA; snRNA, snoRNA, srRNA, and tsRNA have been discovered and found to have novel functions within the cell.  

3. He constructed the 1st viral DNA packaging motor (PNAS, 1986) and concluded that although the parasite depending on the host’s function, the genomic dsDNA of the virus could be packaged in vitro without the help of host factors. The availability of this in vitro artificial motor has served as the model for the study of the mechanisms on viral DNA packaging, as reported in hundreds of subsequent publications in various high-impact journals;   

4. In 1998, he proved the concept of RNA nanotechnology (Mol Cell, 1998; featured in Cell, 1998; 4 papers in Nat Nanotechnol, 2009, 2010, 2011, 2018; Nat Commun, 2019), providing the first evidence that RNA dimers, trimers, tetramers, and hexamers could be constructed via bottom-up self-assembly of multiple reengineered natural RNA molecules.  

5. His team invented a method to use the TIRF System to count single-fluorophores molecules of RNA (EMBOJ, 2007). This single-molecule counting technology has now been applied to the singlemolecule counting of proteins.

6. He developed a unique method for single pore sensing by incorporating a phi29 motor channel into cell membranes (Nat Nanotechnol, 2009).  

7. He utilized RNA nanotechnology to decorate exosomes with ligands for cancer targeting using the directionality of antibody-like (i.e., Y-shaped) RNA arrow-tail (Nat Nanotechnol, 2017)

8. He invented a technology to use RNA as a vector for carrying chemical drugs, and enhance the solubility of paclitaxel for 32 thousand folds and remove the toxicity of paclitaxel in cancer therapy. His lab utilizes ultra-thermostable RNA nanoparticles to deliver chemical prodrugs to address issues with RNA unfolding and nanoparticle dissociation after high-density drug loading. This finding provides a stable nano-platform for chemo-drug delivery as well as an efficient method to solubilize hydrophobic drugs and remove the drug toxicity. Paclitaxel is a popular drug in cancer chemotherapy but toxicity and insolubility have been long a serious concern. Using RNA nanotechnology, his lab improves the solubility of paclitaxel and other chemical drugs by 32 thousand folds and removes the toxicity of paclitaxel in cancer therapy. (Guo S, Vieweger M, Zhang K, Yin H, Wang H, Li X, Li S, Hu S, Sparreboom A, Evers M, Dong Y, Chiu W, Guo P. Ultra-thermostable RNA nanoparticles for solubilizing and high-yield loading of paclitaxel for breast cancer therapy. Nat Commun. 2020 Feb; 972.)

9. His team invented technology for liver cancer therapy by using the special ligand to deliver the paclitaxel and RNA therapeutics to silence the drug efflux pump in the liver cancer cells. His lab designed a new multivalent RNA nanoparticle harboring three copies of hepatocyte targeting ligands, one copy of miR122, and 24 copies of Paclitaxel to overcome the drug effluxion and chemoresistance thus, synergistically treating HCC. The hepatocyte targeting ligands introduce tumor specificity to the RNA nanoparticles as they selectively bind and internalize into liver cancer cells (Wang H, Elliplli S, Lee W, Li X, Vieweger M, Ho Y, Guo P. Multivalent rubber-like RNA nanoparticles for targeted codelivery of paclitaxel and MiRNA to silence the drug efflux transporter and liver cancer drug resistance. J Control Release. 2021 Feb; 173-184).

10. He created methodology for the delivery of cancer drugs to the cytosol of cancer cells without endosome trapping (Zheng Z, Li Z, Xu C, Guo B, Guo P. Folate-displaying exosome mediated cytosolic delivery of siRNA avoiding endosome trapping. J Control Release. 2019 Oct;311-312:43-49). 

11. His team invented Exojuice for exosome purification with a simple one-step procedure involving a combination of zonal and density gradients.

12. He discovered that RNA possesses amoeba and rubbery deformative properties and with unusually efficient capabilities for passive tumor targeting and regression with swift clearance from the kidney, leading to undetectable toxicity levels (Ghimire C, Wang H, Li H, Vieweger M, Xu C, Guo P. RNA Nanoparticles as Rubber for Compelling Vessel Extravasation to Enhance Tumor Targeting and for Fast Renal Excretion to Reduce Toxicity. ACS Nano. 2020 Sep; 13180-13191.).   All inventions 6-11 have enabled his team to develop novel approaches to the treatment of liver cancer; lung cancer, brain cancer, colorectal cancer, breast cancer, stomach cancer, and prostate cancer in preclinical trials (see publication list and news release). ExonanoRNA LLC is actively working to initiate clinical trials for the application of the aforementioned discoveries to the treatment of these cancers.  

13. He discovered the 3rd class of biological ATPase motors using a revolving mechanism without rotation. Biomotors are nanoscale machines ubiquitous in living systems that serve to carry out ATPdriven activities, such as walking, breathing, blinking, mitosis, replication, transcription, and trafficking. Previous studies have identified two types of biomotors: a linear motor and a rotating motor, but Dr. Guo demonstrated the existence of a revolving motor. Instead of rotating like the earth on its axis every 24 hours, this motor revolves like the earth around the sun. The genome in humans and many other living systems are composed of long dsDNA, and if a rotational mechanism is involved, the helical dsDNA will, unfortunately, coil and tangle. However, Dr. Guo discovered that nature had elegantly evolved a revolution mechanism (Schwartz et al., 2013; Zhao et al., 2013) without the use of rotation, coiling, or torque that could even reduce friction.

14. He invented a novel method for the production of the vaccinia virus mRNA capping enzyme (PNAS, 1990 ,7:4023) that is used currently as an essential component for the production of COVID-19 mRNA vaccine.  The capping enzyme is a heterodimer that is required to make the vaccine mRNA stable. Without this mRNA capping enzyme, it is not possible to translate the mRNA into viral protein antigen.  

15. His team invented a patent for the production of COVID-19 mRNA vaccine. This method applies the ligand-displayed exosome to deliver COVID-19 viral mRNA to the cytosol of the antigen processing immune dendritic cell.  The targeted delivery will reduce toxicity. The cytosol delivery will avoid endosome trapping to enhance vaccine efficiency. The method of industry-scale GMP production of the antigenicity-free exosome and a method for the loading of large-mRNA molecules into exosome has also been invented.  

External Links

The Ohio State University - College of Pharmacy

Guo Lab Website

Peixuan Guo Publications

International Society of RNA Nanotechnology and Nanomedicine

Google Patents of Peixuan Guo

Google Scholar Publications of Peixuan Guo