BME Seminar Series: Christopher M. Jewell, Ph.D.

Synthetic Strategies for Overcoming Cell- and Tissue-Level

Ragon Institute Postdoctoral Fellow, Depts. of Materials Science and Biological Engineering, Massachusetts Institute of Technology

Abstract

Drug delivery 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, new clinically-feasible treatments require delivery systems that address both cellular- and tissue-level barriers. In this seminar I will discuss several materials strategies for controlling the delivery of DNA and vaccines in vitro and in vivo. One approach involves delivery of DNA from the surfaces of biomedical devices using nanoscale multilayered films assembled from functional nucleic acids and hydrolytically-degradable polycations. A second strategy allows DNA delivery to be turned ON or OFF in solution by modulating the redox-state of a ferrocene-containing lipid used to condense DNA cargo. At the tissue level, my work has focused on translational studies that target synthetic vaccines to lymph nodes, the control center that coordinates immune response. 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. We are now expanding our work to design vaccines that generate immune responses with tunable characteristics (i.e., immunomodulation) using small molecule drugs, and we are testing this idea to enhance T cell response in HIV vaccines.