This previously postponed preliminary exam has been re-scheduled for December 11.

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 10:00 AM.

Title: DNA Tetrahedron Design Optimization for Efficient Drug Delivery Through the Blood-Brain Barrier

Date: Monday, December 11

Time: 10:00 AM

Location: MJIS 1001

Advisory Committee: Leopold N. Green, Co-Chair; Tamara L. Kinzer-Ursem, Co-Chair; Chengde Mao; Gregory T. Knipp

Abstract:

Studying, treating, and mitigating the symptoms of Alzheimer’s Disease and other Neurodegenerative Disorders is a big challenge due to the low Blood-Brain Barrier (BBB) permeability, which is highly selective on what can pass into the brain. In the proposed study, I aim to address the lack of a safe, efficient, and reliable brain drug delivery vehicle by optimizing the design of Tetrahedral DNA Nanomaterials (TDNs) to effectively deliver drugs through the BBB. Starting with two classical TDNs structures, I alter the design by changing the size, structure (one or two double-stranded DNA helices on the edges), and attached DNA aptamers for the receptor-medicated endocytosis pathway. I will study the influence of these factors on cellular uptake, stability of TDNs, toxicity, and potential delivery efficiency. I plan on testing the materials in vitro using primary mice cortical cells and human astrocytes Isogenic-induced Pluripotent Stem Cells, as well as in the human BBB in vitro model. To study the biodistribution and tissue toxicity, I will perform in vivo tests of the most promising TDNs designs in the C57BL/6 wild-type mouse model, harvest the tissues, and run histology analysis with Hematoxylin and Eosin Y stains. The TDNs concentration will be measured by using incorporated into the DNA strands cyanine 3 and 5 dyes fluorescence and the stability will be estimated by Fluorescence Resonance Energy Transfer measurements. After this work, I will have developed an effective, exceptionally biocompatible, and stable nanomaterial with great potential applications in drug delivery through BBB, brain imaging, and gene therapy.