Wenhui Hu
Virginia Commonwealth University, VA·Microbiology & Immunology
Antiretroviral drugs can keep HIV undetectable in the blood, but they cannot remove the viral DNA that has inserted itself into a patient's own chromosomes. Those silent copies sit inside long-lived cells and restart infection whenever treatment stops.
- Fields
Microbiology & Immunology
Neuroscience
Pharmacology
- Topics
HIV cure
latent reservoir
provirus excision
- Grants
- 2 known grants, through Nov 2027
What they work on
- Show that brain-penetrating AAV can deliver cargo to astrocytes and neurons that then relay it to untouched microglia, using PEG10- and syncytin-A-based endogenous retrovirus-like particles carrying Cre messenger RNA in LoxP-STOP-LoxP tdTomato reporter mice that turn red when edited.
- Measure how efficiently the combined exosome and retrovirus-like particle system, using CD63 fused to a microglia-targeting peptide, delivers multiplexed Cas12f — a miniature CRISPR enzyme — and its guide RNAs into microglia of reporter and HIV Tg26 transgenic mice.
- Test whether systemic injection of the brain-penetrating AAV Cas12f delivery system reduces HIV provirus and associated neuroinflammation in HIV Tg26 transgenic mice.
- Optimize VSVG-pseudotyped lentivirus-like particle resicles that carry Cas12a as ribonucleoprotein or messenger RNA, loaded via the MS2 coat protein, to excise HIV proviral DNA and the entry co-receptor CCR5 in cells and in mice.
- Engineer CD4-targeted delivery particles using DARPins, small designed binding proteins, or HIV envelope protein, and test their editing efficiency in human CD4 T cells, the main latent HIV reservoir.
- Evaluate whether CD4-targeted particles delivering multiplexed Cas12a excise HIV provirus and knock out CCR5 in HIV-infected, antiretroviral-suppressed humanized BLT mice carrying a human immune system.
More about the research
Gene-editing tools such as CRISPR can, in principle, cut that integrated provirus out of the genome; the stubborn obstacle is delivery — getting the molecular scissors into the specific cells that harbor the virus, inside a living body, without hitting everything else. Both projects in this lab attack that delivery problem, one aimed at the brain and one at immune cells in the blood and tissues.
Why it matters
There is no cure for HIV because the virus hides as DNA inside long-lived cells, including microglia in the brain and CD4 T cells, and persists even on effective antiretroviral therapy. Delivery systems that carry CRISPR editors to exactly those cells in a living body could enable strategies that cut out the integrated provirus and disable the CCR5 entry receptor, and the same targeting tools could be adapted for other diseases of microglia or T cells.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Angela Raquel Wahl
University of Alabama at Birmingham, AL·Microbiology & Immunology
Analyze how the HIV reservoir forms in the gastrointestinal tract of BLT humanized mice on antiretroviral therapy, measuring HIV DNA and transcripts in gut CD4+ T cells compared with blood.
Jeremy Luban
University of Massachusetts Chan Medical School, MA·Microbiology & Immunology
Identify host factors required for HUSH-mediated silencing of the HIV-1 provirus using unbiased genome-wide loss-of-function screens, then test mechanistic hypotheses for how each factor contributes.
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
Virginia Commonwealth University: 19 labs on PI Pages, $524M a year on research, 438 research doctorates a year.
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