David Curiel
Washington University in St Louis, MO·Microbiology & Immunology
Curing HIV may require giving the immune system a weapon it rarely makes on its own: antibodies that can neutralize many different strains of the virus at once. One way to do that is to rewrite the DNA of a patient's own antibody-producing cells, B cells, so they manufacture these broadly neutralizing anti-HIV antibodies.
- Fields
Microbiology & Immunology
Genetics
Medicine & Clinical Research
- Topics
gene therapy
vectored immunotherapy
B cells
- Grants
- 1 known grant, through Dec 2028
What they work on
- Develop replication-defective adenoviral vectors that transduce B cells efficiently and selectively inside the body, using a "triple targeting" design intended to restrict gene delivery to the intended target cells.
- Use adenovirus to co-deliver CRISPR/Cas9 editing machinery and donor DNA so that broadly neutralizing anti-HIV antibody genes integrate at a precise genomic site via homology-directed repair, the cell's template-guided DNA repair pathway.
- Engineer B cells to express anti-HIV broadly neutralizing antibodies as functional antigen receptors spliced to the cell's own heavy-chain constant genes, so edited cells can expand and mature normally.
- Build vectors from non-human primate adenoviruses to bypass pre-existing human immunity against common adenoviral vectors, and assess whether in vivo B-cell editing can be achieved with an acceptable safety margin.
More about the research
This work develops the delivery technology needed to make that genetic rewrite happen inside the body rather than in a laboratory dish.
Why it matters
There is no cure for HIV, and antibodies that neutralize many viral strains are hard for the body to produce. By engineering a patient's own antibody-producing cells inside the body instead of in a laboratory, this work could make antibody-based gene therapy for HIV simpler, cheaper and available to more people. The targeted adenoviral vectors developed here may also serve as delivery tools for other gene-editing therapies.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Allison Keeler-Klunk
University of Massachusetts Chan Medical School, MA·Microbiology & Immunology
Determine how adeno-associated virus-delivered CRISPR-Cas9 provokes B- and T-cell responses against Cas9 that clear edited cells, comparing dual-AAV delivery with an AAV plus lipid nanoparticle approach that expresses Cas9 only transiently.
Matthew Gardner
Emory University, GA·Microbiology & Immunology
Test whether co-delivering an AAV vector encoding rhesus macaque PD-L1, a protein that engages the T-cell brake receptor PD-1, sustains blood levels of the HIV broadly neutralizing antibody 10-1074 high enough to protect macaques from repeated low-dose SHIV challenge.
Harris Goldstein
Albert Einstein College of Medicine, NY·Microbiology & Immunology
Build and optimize injectable lentiviral vector particles retargeted to CD3, a marker on T cells, so they transduce T cells directly inside the body and turn them into anti-HIV duoCAR-T cells without lab manufacturing.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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