Biophysical Society Thematic Meeting | Ascona, Switzerland

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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery Friday Speaker Abstracts
48
Membrane Decoys as Anti-Viral Nanomedicine
Roy Ziblat1, Sarah Stubbs2 , Xuling Zhu2, Sean Whelan 2, Priscilla Yang2 .David Weitz1,3,
1Harvard University, Cambridge, MA, USA, 2Harvard University, Boston, MA, USA, 3Harvard
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
No Abstract