Yizhou Dong
Icahn School of Medicine at Mount Sinai, NY·Pharmacology
Genetic medicines can switch a gene off or supply a missing protein, but only if the drug reaches the right cells. Getting these fragile nucleic acids into the body intact, past the barriers that protect the brain, and into one tissue rather than another is the central obstacle.
- Fields
Pharmacology
Biomedical Engineering
Chemistry
- Topics
lipid nanoparticles
mRNA delivery
antisense oligonucleotides
- Grants
- 5 known grants, through May 2031
What they work on
- Design and synthesize blood-brain barrier-crossing conjugates that link brain-penetrant small molecules to antisense oligonucleotides, and test how they move through barrier cells using transcytosis and mechanistic assays.
- Develop chemically modified antisense oligonucleotides against transcription factors identified in postmortem human brain and mouse models of cocaine use disorder, then test the conjugates for efficacy and safety in mice that self-administer cocaine.
- Synthesize barrier-crossing lipid nanoparticles, identify lead formulations, and trace their trafficking routes into the brain in mice before measuring delivery efficiency and safety in non-human primates.
- Engineer small interfering RNA to lower APOE4 and messenger RNA to raise APOE2, deliver them with receptor-targeted nanoparticles, and evaluate therapeutic effect, pharmacokinetics and brain uptake in mouse Alzheimer's models using PET and MRI.
- Build adjuvant-derived nanoparticles from toll-like receptor and STING agonists, immune-sensor activators, and pair them with messenger RNAs encoding HIV antigens optimized through engineered untranslated regions.
- Determine the antibody and T-cell responses and safety of the nanoparticle-mRNA HIV vaccine candidate in mouse and non-human primate models.
- Optimize four lipid chemistries, TT, vitamin-derived, glycolipid and novel derivatives, to direct messenger RNA to liver cells, macrophages, stem cells and reproductive cells respectively, and test delivery and safety in animals.
More about the research
Work here designs the carriers and the cargo together: new lipid molecules that self-assemble into nanoparticles, chemical tags that help a drug cross into the brain, and engineered RNA sequences that boost protein output or avoid the liver. These tools are then tested against specific problems, including cocaine use disorder, Alzheimer's disease, HIV vaccination, and cell-specific delivery for diseases such as hemophilia and drug-resistant infection.
Why it matters
No medication is approved for cocaine use disorder, and Alzheimer's disease and HIV remain without adequate treatments or a vaccine. Carriers that move RNA drugs safely across the blood-brain barrier, or into a chosen cell type such as liver cells or macrophages, could make gene-silencing and protein-replacement therapies usable for brain disorders, inherited bleeding disorders like hemophilia A, and drug-resistant bacterial infections, and could speed vaccine design for emerging pathogens.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yamin Li
Upstate Medical University, NY·Pharmacology
Expand the chemical diversity of sulfonium lipids — carriers that use a charged sulfur group instead of the usual amine — by adding new head, linker and tail building blocks, and relate these structures to self-assembly, mRNA delivery and biocompatibility.
Byron Purse
San Diego State University, CA·Chemistry
Create ASO and siRNA stand-ins carrying a pair of fluorescent ribonucleosides, one a steady reference and one pH-sensitive, to image cell uptake and measure escape from acidic endosomes in live cells.
Howard E Gendelman
University of Nebraska Medical Center, NE·Microbiology & Immunology
Scale up and characterize long-acting injectable nanoformulated prodrugs of dolutegravir, emtricitabine and tenofovir (NM2DTG, NPFTC, NPTFV) under cGMP manufacturing, testing toxicology and pharmacokinetics in rhesus macaques for HIV prevention dosing up to once yearly.
The school
Icahn School of Medicine at Mount Sinai: 45 labs on PI Pages, $1.0B a year on research, 62 research doctorates a year.
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