Reza Shahbazi
Indiana University-Purdue University-Indianapolis, IN·Biomedical Engineering
Sickle cell disease and beta thalassemia arise from faults in adult hemoglobin, the protein that carries oxygen in red blood cells. A promising workaround is to restart production of fetal hemoglobin, the version made before birth, which can substitute for the defective adult form.
- Fields
Biomedical Engineering
Pharmacology
Genetics
- Topics
gene editing
ribonucleoprotein
lipid nanoparticles
- Grants
- 1 known grant, through Apr 2031
What they work on
- 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.
- Encapsulate CRISPR in its ribonucleoprotein form, the preassembled Cas protein and guide RNA, within these Exo-CRISPR nanoformulations and test delivery efficiency and targeting specificity.
- Test whether Exo-CRISPR nanoformulations can disrupt the BCL11A binding site on the gamma-globin gene and induce fetal hemoglobin production as a substitute for defective adult hemoglobin.
- Evaluate in vivo CRISPR delivery as an alternative to the current ex vivo route, in which CD34-positive cells are isolated and edited by electroporation outside the body.
More about the research
CRISPR gene editing can accomplish this by disrupting the site on the gamma-globin gene where BCL11A, a protein that normally silences fetal hemoglobin, binds. The edit has to reach hematopoietic stem cells, the bone marrow cells that generate every blood cell type, and especially long-term hematopoietic stem cells, the subset that renews itself indefinitely. Current practice removes CD34-marked cells from the patient and edits them outside the body using electroporation, brief electrical pulses that open the cell membrane. That route is slow, expensive, specific to no particular stem cell subset, and confined to well-equipped facilities, which is a poor match for the regions where most beta hemoglobinopathies occur. Some patients' cells are also unsuitable for the procedure.
Why it matters
An injectable gene-editing delivery system would remove the need to harvest, edit, and transplant a patient's own stem cells, the step that makes current CRISPR therapy for sickle cell disease and beta thalassemia costly and available only at specialized centers. If successful, this could widen access to treatment in resource-limited regions, where most people with these inherited blood disorders live, and could serve patients whose cells are unsuitable for laboratory editing.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Gordon Ginder
Virginia Commonwealth University, VA·Biochemistry
Determine how mutations that break the contact between the GATAD2A CR-2 region and the C-terminal pocket of CHD4, the DNA-repackaging motor of the NuRD complex, affect fetal hemoglobin output in adult-type human red blood cell precursors.
Emery H. Bresnick
University of Wisconsin-Madison, WI·Genetics
Test whether GATA2 and C/EBPε, a factor that drives granulocyte formation, work together and separately to set up progenitor gene activity, using GATA2 activation of a Cebpe enhancer as the entry point.
Kiana Aran
University of California-San Diego, CA·Biomedical Engineering
Design CRISPR-transistor sensors that use a range of guide RNAs and Cas nucleases to electronically detect single-letter DNA changes, using the sickle cell HBB mutation as the model.
The school
Indiana University-Purdue University-Indianapolis: 25 labs on PI Pages, $89M a year on research, 120 research doctorates a year.
More about Indiana University-Purdue University-Indianapolis
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