David Scadden
University of Southern California, CA·Biomedical Engineering
Making a person's own blood-forming cells resistant to HIV is an appealing idea, but current routes are demanding: they generally require a stem cell transplant, or they rely on gene-delivery vectors injected throughout the body, where they can reach organs that were never meant to be modified. This project tests a different strategy, growing a small, accessible patch of bone and bone marrow just under the skin and using it as a delivery portal for anti-HIV genetic constructs.
- Fields
Biomedical Engineering
Microbiology & Immunology
Medicine & Clinical Research
- Topics
bone marrow organoid
hematopoietic stem cells
blood progenitor cells
- Grants
- 1 known grant, through Jun 2030
What they work on
- Test whether a bioinstructive material can form bone and functional bone marrow at a localized, easily accessible subcutaneous site that serves as a delivery portal for gene-modifying vectors.
- Tune the marrow organoid to produce the specific blood cell subsets required by the different anti-HIV genetic constructs developed in partner projects of the program.
- Determine whether locally administered, low-dose gene-engineering vectors can modify blood stem and progenitor cells in the organoid without hematopoietic stem cell transplantation or systemic vector delivery.
- Evaluate whether the strategy generates HIV-1-resistant stem and progenitor cells in humanized mice and in non-human primates.
More about the research
The approach uses a bioinstructive material, a scaffold whose composition prompts surrounding cells to form bone and marrow tissue at a localized subcutaneous site. Because that engineered marrow organoid sits near the surface, gene-modifying vectors can be applied locally in small amounts, lowering the quantity of material needed and reducing the chance of modifying other organs. Blood stem and progenitor cells, the cells that renew the blood and immune system, would then be engineered in place rather than removed, modified and transplanted back. The organoid will be tuned to produce the particular cell subsets that suit the different anti-HIV constructs being developed by partner projects in the same program. Whether this strategy actually yields HIV-1-resistant stem and progenitor cells will be tested in humanized mice, mice carrying a human blood and immune system, and in non-human primates, in collaboration with other investigators in the program.
Why it matters
Gene therapies that make blood cells resistant to HIV-1 currently depend on hematopoietic stem cell transplantation, a procedure too risky and costly for broad use. An accessible subcutaneous marrow organoid could allow such cells to be engineered in place with far less vector, potentially lowering cost and limiting unintended modification of other tissues, a route that may eventually widen access to HIV gene therapy.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Teresa V Bowman
Albert Einstein College of Medicine, NY·Genetics
Test whether DDX41 insufficiency cooperates with age-associated activity of cGAS, an inflammation-triggering DNA sensor, to impair blood stem and progenitor cells in germline ddx41 heterozygous zebrafish that develop MDS-like disease.
Xuefang Cao
University of Maryland, Baltimore, MD·Microbiology & Immunology
Determine whether blood-forming stem and progenitor cells use the receptor CD27 to directly suppress donor T cells, using transplants into Rag1 knockout mice that lack CD27 and NK cells, in vivo and in vitro.
Gerard Madlambayan
Oakland University, MI·Biology
Test whether binding between the integrin CD49f and laminins in the tumor extracellular matrix keeps hematopoietic stem and progenitor cells functional in tumors, by blocking or enhancing this interaction in vitro and in vivo.
The school
University of Southern California: 47 labs on PI Pages, $1.3B a year on research, 882 research doctorates a year.
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