Nienhuis: Development of gene therapy for hematopoietic disorders

My research is focused on the development of gene therapy for hematopoietic disorders. We are testing lentiviral vectors based on HIV which have inherent biological advantages for transfer of genes into blood stem cells. Molecular engineering allows the design of vectors which carry the gene of interest without risk of HIV infection.

In collaboration with Dr. Derek Persons, much of our research focused on development of vectors capable of supporting high levels of globin gene expression in developing erythroblasts. Recent work has shown that we can achieve therapeutic levels of vector encoded fetal hemoglobin in the red blood cells that arise from stem cells obtained from patients with beta-thalassemia. Similar studies are being done with lentiviral vectors designed to correct cell defects in patients with Wiskott-Aldrich Syndrome.

Our work has also focused on the development of gene therapy for Factor IX deficiency in collaboration with Dr. Andrew Davidoff, Chair of the Department of Surgery. This work has culminated in a successful clinical trial in which we have shown that our recombinant adeno-associated viral vector allows stable long-term production of human FIX in patients with hemophilia B. The vector is given only once as an intravenous infusion with vector particles transferring and expressing the FIX gene in the liver.