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Codon Optimization> | The T cell receptor (TCR) alpha chain leader was put upstream, the sequence for the CD28 transmembrane and intracellular region and the intracellular domain of the CD3 zeta chain were put downstream of the scFv-IgG1 sequence. The designed ANS8 CAR construct was codon-optimized and synthesized by GenScript USA (Piscataway, NJ) and ligated into the retroviral pRetroX-IRES- ZsGreen1 vector (Clontech, Mountain View, CA). | Get A Quote |
Replacement therapy with factor VIII (FVIII) is used in patients with hemophilia A for treatment of bleeding episodes or for prophylaxis. A common and serious problem with this therapy is the patient's immune response to FVIII, because of a lack of tolerance, leading to the formation of inhibitory antibodies. Development of tolerogenic therapies, other than standard immune tolerance induction (ITI), is an unmet goal. We previously generated engineered antigen-specific regulatory T cells (Tregs), created by transduction of a recombinant T-cell receptor (TCR) isolated from a hemophilia A subject's T-cell clone. The resulting engineered T cells suppressed both T- and B-cell effector responses to FVIII. I... More