Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Friday Speaker Abstracts

Membrane Decoys as Anti-Viral Nanomedicine Roy Ziblat 1 , Sarah Stubbs 2 , Xuling Zhu 2 , Sean Whelan 2 , Priscilla Yang 2 .David Weitz 1,3 , 1 Harvard University, Cambridge, MA, USA, 2 Harvard University, Boston, MA, USA, 3 Harvard University, Cambridge, MA, USA. Humans are locked in an evolutionary struggle with viruses. As population density rises the risk of new pandemics is ever increasing and there is high demand for anti-viral drugs. Viruses carefully choose host cells, infiltrate through their membranes, and disrupt cell activity by hijacking their protein machinery for viral replication. The main therapeutic approaches are by interrupting the viral life cycle using bio-molecular inhibitors, or by vaccination, which helps the immune system to fight off the virus. Vaccines, however, are not effective against rapidly mutating viruses and have little therapeutic value to patients already infected. In this study, a novel therapeutic approach is proposed whereby viruses are induced to fuse with a “decoy” membrane before ever encountering the host cell. Lipids, from which the cell membranes are composed, differ significantly according to cell type and organelles they encompass. The selectivity of the virus to fuse with the specific host cell is lipid dependent. When designing a decoy membrane, the challenge is, therefore, to identify for every type of virus its matching lipid compositions. To address this challenge, we have developed a unique microfluidic setup that enables high-throughput screening over a large library of membranes to identify a lipid selectivity profile for any target protein, including the viral proteins that interact with the cell membrane. The library is composed of over 200 membranes and is 7-fold larger than any previously reported library. Using this methodology, we generated lipid selectivity profiles for dengue, ebola and influenza viruses, and in each case were able to identify distinct lipid compositions that are recognized with high affinity and selectivity even without the presence of a receptor protein. We demonstrate that by using the nano-decoys, the infectivity of cells exposed to the virus is diminished significantly.

Exosomes Sufficiently Deliver Secreted Small RNA to Recipient Tissues

Chen-Yu Zhang Nanjing University, Nanjing, Jiangsu, China

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