Event
Bioengineering Seminar Series: Christopher M. Jewell
Friday, December 9, 2011
11:00 a.m.
Room 1200 Jeong H. Kim Engineering Bldg.
Professor Silvia Muro
muro@umd.edu
Synthetic Strategies for Engineering Biological Response
Christopher M. Jewell
Departments of Materials Science Engineering and Biological Engineering
Massachusetts Institute of Technology
Ragon Institute of MGH, MIT, and Harvard
Drug delivery the time, location, and specificity with which biological cargo is delivered continues to create challenges in medicine. These obstacles encompass tissue-level barriers such as ensuring cargo reaches the correct organs or tissues at appropriate concentrations, and cell-level barriers including cell internalization and endosomal escape. Thus, developing new clinically-feasible treatments requires delivery systems that address both cellular- and tissue-level barriers. My research involves the design and exploitation of synthetic materials to achieve high levels of control over the delivery of biological cargo, and more sophisticated control over drug delivery provides new opportunities to engineer or tune biological outcomes (e.g., immune response). In this seminar I will discuss several strategies for controlling the delivery of DNA and vaccines in vitro and in vivo. One strategy involves delivery of DNA from the surfaces of biomedical devices using nanoscale multilayered films assembled from functional nucleic acids and hydrolytically-degradable polycations. We have also developed a strategy for turning DNA delivery ON or OFF in bulk solution by self-assembly of complexes formed from DNA and a ferrocene-containing lipid that exhibits a net charge that can be modulated between +1 (reduced, ON) and +3 (oxidized, OFF). I will conclude the seminar with some of my recent work focused on translational studies involving synthetic vaccines. In this work we have combined intra-lymph node delivery which has recently demonstrated great potential in human clinical trials with biomaterial vaccine depots to generate extremely potent cellular immune responses for therapeutic vaccination. We have also expanded our work to preventative vaccines that allow generation of immune responses with tunable characteristics (i.e., immunomodulation) using small molecule drugs, and we are testing this strategy as a route for enhancing T cell vaccines for HIV.