Peixuan Guo
Ohio State University, OH·Pharmacology
Colon cancer is the second leading cause of cancer death, and much of that toll comes from tumors carrying mutations in KRAS, a gene whose protein drives uncontrolled cell growth. Mutant KRAS has long been called "undruggable," and once the disease spreads to the lung, survival is often measured in months.
- Fields
Pharmacology
Biomedical Engineering
Biochemistry
- Topics
mutant K-Ras
colorectal cancer
colon cancer
- Grants
- 1 known grant, through Jun 2029
What they work on
- Define the conditions for assembling the dCas9-HDAC1 fusion repressor with guide RNA or crRNA, including sequence and length requirements, that most effectively silence mutant KRAS and suppress colon cancer cells.
- Load the preassembled dCas9-HDAC1-gRNA ribonucleoprotein complex into exosomes and determine the mechanism by which it represses the mutant KRAS promoter through epigenome editing.
- Engineer RNA nanoparticles displaying colon-cancer-binding aptamers on exosome surfaces, and test whether higher ligand density and more negative zeta potential reduce uptake by healthy cells and vital organs.
- Test whether RNA-ligand-displaying exosomes carrying the dCas9-HDAC1 ribonucleoprotein, mutant K-Ras siRNA, and the drug SN-38, alone or combined, inhibit primary and lung-metastatic colorectal tumors in orthotopic and patient-derived xenograft mouse models.
- Determine how RNA ligand design and selection of sub-100 nm exosomes by density gradient ultracentrifugation or size exclusion improve endosome escape, biodistribution, and escape from macrophage engulfment.
More about the research
This project builds a delivery system that can carry large gene-silencing machinery directly into colon cancer cells and shut mutant KRAS down.
Why it matters
Mutant KRAS drives up to 45% of colorectal cancers and has resisted conventional drugs, while metastatic disease responds poorly to chemotherapy. A delivery system that carries large protein–RNA complexes specifically into tumor cells could offer a route to silencing this target with less toxicity to healthy tissue, and more broadly a way to deploy bulky gene-regulating machinery against other hard-to-drug cancer targets.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dan Shu
Ohio State University, OH·Biomedical Engineering
Build and evaluate exosome–RNA nanoparticle complexes carrying TNBC-targeting ligands, including RNA aptamers against EGFR, CD133, CD44 or nAHRs and the chemical ligand methotrexate, together with tumor-suppressing siRNA and miRNA cargo.
Shi-He Liu
University of Toledo, OH·Biomedical Engineering
Evaluate whether exosomes displaying both the tumor-homing peptide RGD and the CD47 "don't eat me" peptide on surface protein CD9 (ExoSmart) target pancreatic cancer, using stroma-rich 3D human tumor spheroids in vitro and in vivo.
Reza Shahbazi
Indiana University-Purdue University-Indianapolis, IN·Biomedical Engineering
Engineer biomimetic lipid nanoparticles that incorporate exosome components shown to interact specifically with long-term hematopoietic stem cells, the self-renewing bone marrow cells that produce all blood cell types.
The school
Ohio State University: 71 labs on PI Pages, $1.6B a year on research, 882 research doctorates a year.
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