PROJECT SUMMARY Cell therapies are living drugs that can access a multifaceted biological response and can therefore potentially provide not only therapeutic but also regenerative outcomes. However, these beneficial attributes of cell therapeutics are accompanied by significantly more complex, variable, and costly production logistics. Major advances in biomanufacturing are required for cell therapies to have broad and widespread use. In this application, we propose to develop aptamer-based technologies for cell separation that will provide an impactful improvement over current technology, resulting in superior product at a fraction of the cost. Our main objectives are to 1) establish a novel SELEX method for membrane proteins and identify new aptamers for cell isolation applications, 2) develop methods for traceless isolation of monocytes and generation of macrophage and dendritic cell products for immunotherapy, 3) demonstrate multiplexed selection and T cell subset selection for CAR T cell immunotherapy applications, and 4) enable efficient collection and expansion of urine stem cells as a source for regenerative medicine therapies. Successful completion of these aims will lead to a platform technology for scalable and more affordable production of CAR T cell immunotherapy, monocyte-based cell therapies and stem cell treatments.