Arun Srivastava
University of Florida, FL·Medicine & Clinical Research
Gene therapy puts a working copy of a faulty gene into a patient's cells, and one common delivery vehicle is adeno-associated virus (AAV), a virus that causes no known disease in humans. Current AAV vectors often enter their target tissues inefficiently, so very large doses are needed, which raises cost and the risk of immune reactions.
- Fields
Medicine & Clinical Research
Genetics
Microbiology & Immunology
- Topics
gene therapy
adeno-associated virus
AAVrh74
- Grants
- 2 known grants, through Nov 2028
What they work on
- Develop liver-de-targeted, capsid- and genome-modified next-generation AAV vectors based on AAVrh74 for skeletal muscle and AAV9 for the central nervous system, and demonstrate enhanced expression from AAV-PDHA1 vectors.
- Test safety and efficacy of combining the oral drug dichloroacetate (DCA) with AAVrh74- and AAV9-PDHA1 gene transfer in a mouse model of pyruvate dehydrogenase complex deficiency.
- Determine the molecular mechanism by which engineering the inverted terminal repeats (ITRs), the DNA ends flanking the delivered gene, increases transgene expression from AAV vectors.
- Evaluate ITR-engineered AAV3 vectors, the serotype most efficient in primary human hepatocytes, for liver gene transfer in cultured human hepatocytes and in humanized mice.
- Test whether ITR-engineered AAV8 vectors correct the bleeding phenotype in mouse models of hemophilia A and B, and measure how immunogenic these vectors are.
More about the research
Both projects here engineer better AAV vectors by changing the protein shell (capsid) and the vector's DNA ends, and then test them in disease models: one for an inherited energy-metabolism disorder in children, the other for the bleeding disorders hemophilia A and B.
Why it matters
Children with pyruvate dehydrogenase complex deficiency currently have no FDA-approved therapy, and a combined drug-plus-gene approach could offer a treatment route for this fatal disease. For hemophilia A and B, vectors that work at lower doses may reduce the need for immune-suppressing drugs, improve safety, and lower production costs, which matters for making liver-directed gene therapies more widely accessible.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Xin Chen
University of Texas Southwestern Medical Center, TX·Genetics
Test whether AAV9fyhr-delivered PDHA1, injected into the spinal fluid of E75A mice at several doses and at young or older ages, improves behavior and corrects metabolic measures in this model of pyruvate dehydrogenase complex deficiency.
Aravind Asokan
Duke University, NC·Biomedical Engineering
Test whether IceMG, an engineered protease that cleaves human and monkey IgG and IgM antibodies, blocks complement activation and modulates B-cell signaling, using human cell models, humanized mice and non-human primates.
Renzhi Han
Indiana University-Purdue University-Indianapolis, IN·Pharmacology
Develop an improved triple-vector system in next-generation myotropic adeno-associated virus capsids to reconstitute full-length dystrophin by protein trans-splicing across skeletal, diaphragm, and heart muscle in models of Duchenne muscular dystrophy.
The school
University of Florida: 65 labs on PI Pages, $1.3B a year on research, 795 research doctorates a year.
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