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Compact Gene Regulatory Cassettes Support Hallmark Features Of T-Cell Receptor (Tcr)-Alpha Gene Locus Control Region (Lcr) Activity, Jordana Lovett

Dissertations, Theses, and Capstone Projects

Despite the promise of emerging stem cell transplant gene therapy strategies, there remains a gap in the ability to predictably generate robust, temporally controlled long-lasting, therapeutic gene expression in specific target cell lineages following stem cell differentiation. There exists a locus control region (LCR) in the mouse T-cell receptor (TCR)-α locus that confers an ab TCR-like spatiotemporal expression pattern upon a linked transgene, regardless of its site of integration in the genome. These properties are well suited to direction of high-level, physiological expression of therapeutic antigen receptor genes to the T cell progeny of vector-transduced stem cells. The endogenous LCR …