Passey, Abigail; Domyan, Eric (Utah Valley University)
Faculty Advisor: Domyan, Eric (Utah Valley University, Department Of Biotechnology/Biology)
In the United States approximately 3 million people are living with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Approximately 75,000 of those patients represent pediatric cases. We aim to create a new drug delivery system with the intention of establishing a more feasible, stable, and effective form of administering treatments to those with the aforementioned autoimmune diseases, specifically attempting to provide a more ideal treatment for juvenile patients. We are focusing on first providing a rudimentary proof of concept. For the project, we will attempt to engineer mammalian cells that will produce the fusion protein CTLA4-Ig, commonly known as abatacept, a current treatment for RA, and a potential treatment for SLE. Thus far, we have completed and verified success of the molecular cloning necessary to create the recombinant molecule. We have successfully induced expression of the fusion protein in mammalian cell lines COS-7 and B16F10 via lipofections. We are currently working to optimize lipofection conditions and test for successful cellular production of CTLA4-Ig. Ideally, we aim to engineer red blood cells (RBCs) to produce the molecule. If we can complete our proof of concept, we will then attempt to reprogram myeloid and lymphoid progenitors into induced hematopoietic stem cells (iHSCs), and culture the cells ex vivo to allow for massive expansion of these iHSCs, which can then be genetically engineered. Additionally, the iHSCs will be cultured in such a way that, once in vivo, will result in them committing explicitly to erythroid lineages, and secreting the target protein as they mature into fully functional, adult RBCs. Causing RBCs to secrete CTLA4-Ig throughout the body would eliminate the need for regular injections of the drug, and thus potentially improve the quality of pediatric patients' lives.