CAREER: Synthetic Design and Biological Study of Novel Polymeric DNA Delivery Vehicles

With the support of the Organic and Macromolecular Chemistry Program in the Chemistry Division and the Biomolecular Systems Program in the Molecular and Cellular Biosciences Division, Professor Theresa Reineke of the University of Cincinnati will identify how the presence of hydroxyl groups, the number of amine centers, the density of the cationic charge centers, the charge center type, and the geometry of polymeric materials promote effective nucleic acid binding, and she will determine how the chemical and structural properties detailed above affect cytotoxicity, intracellular delivery, and gene expression within living cells. The development of efficient and nontoxic nucleic acid delivery vehicles has become one of the most significant and fundamental problems facing research fields involving gene function, cellular signaling, gene therapy, genetic vaccines, and plant biotechnology. Due to the dangers associated with virus-based delivery systems, polymeric vectors now show great promise. However, problems with toxicity, low delivery efficiency, and a lack of insight into the polymer structure-biological property relationships have hampered their use. The goals of the proposal will be accomplished by synthesizing five novel polymer families that vary in the functionalities mentioned above and by studying the polymer-DNA interactions via isothermal titration calorimetry, dynamic light scattering, and zeta potential measurements. Lowry protein, beta-galactosidase, and luciferase gene expression assays will be performed with a variety of cell lines transfected with the new polymers.

The Organic and Macromolecular Chemistry Program and the Biomolecular Systems Program in the Molecular and Cellular Biosciences Division supports Professor Theresa Reineke of the University of Cincinnati who will establish and promote interactive mentoring, cooperative learning, and research programs that successfully unite teaching and scholarship. This will be completed through developing a structured mentoring program called Emerging Ethnic Scientists (EES) that incorporates interactive and cooperative learning techniques into a Freshman Chemistry course and mentoring high school and undergraduate students in the process of scientific research. The long-range goals and broader impacts of this work are to formulate a design model that can be utilized by researchers in the field of polymeric gene delivery to develop efficient and nontoxic vectors for specific cell types and applications and impart to students the excitement of performing interdisciplinary research with the goal of increasing the retention of underrepresented groups in the sciences. Students involved in this interdisciplinary program will gain a uniquely broad and in-depth experience in several areas ranging from synthetic chemistry and polymer science to molecular biology.