BME PhD Preliminary Exam Announcement for Grigorii Rudakov (T. Kinzer-Ursem and L. Green, Co-Advisors) Everyone is invited to attend the public presentation beginning at 9:00 am. For coffee and bagels come 15 minutes early. Title: DNA Tetrahedron Design Optimization for Efficient Drug Delivery Through the Blood-Brain Barrier Date: November 9, 2023 Time: 9:00 am Location: MJIS 2001 Committee: Dr. Tamara Kinzer-Ursem (co-chair), Dr. Leopold Green (co-chair), Dr. Chengde Mao (Chemistry), Dr. Gregory Knipp (Pharmacy) Abstract: In our proposed study, we aim to optimize the design of Tetrahedral DNA Nanomaterials (TDN) to effectively deliver drugs through the Blood-Brain Barrier (BBB). Starting with two classical TDN structures, we alter the design by changing the size, structure (one or two double-stranded DNA helices on the edges), and attached DNA aptamers for receptor-medicated endocytosis pathway to study the influence of these factors on cellular uptake, stability of TDNs, toxicity, and potential delivery efficiency. We plan on testing our materials in vitro HEK293, SUM159, mice cortical, and human astrocytes cellular lines, as well as in the human BBB in vitro model. To study the biodistribution and tissue toxicity, we will perform in vivo tests of the most prominent TDNs designs on the C57BL/6-wt mouse model, harvest the tissues, and run histology analysis with H&E stains. The TDNs concentration will be measured by measuring implemented into the DNA strands cyanine 3 and 5 dyes fluorescence and the stability will be estimated by Fluorescence Resonance Energy Transfer measurements. If we succeed in our work, we will develop an effective, exceptionally biocompatible, and stable nanomaterial with great potential applications in drug delivery through BBB, brain imaging, and gene therapy. We expect the main application of this nanomaterial to be in treating and mitigating the symptoms of Alzheimer's and other neurodegenerative diseases, as the low BBB permeability poses the main challenge in the way of studying and treating these illnesses.