While viruses are primarily known as pathogens, we still can benefit from their own advances. They have been extensively used for genetic transfection, virotherapy, vaccines, drug delivery, imaging agents, and materials science. Despite these successes, bottom-up anti-virus biomolecular engineering still presents three substantial challenges: membrane protein, complex assembly, and bioconjugation. Here we adopt a cell-free synthetic biology strategy to address those three challenges. Cell-free synthetic biology is emerging as a powerful interdisciplinary bioengineering approach aimed to harness and expand the capabilities of natural biological systems without using intact cells. It enables proper folding of viral membrane protein, expression of proteins toxic to cells, fast high-throughput screening, controllable virus particle assembly, and incorporation of unnatural amino acids into proteins for bioorthogonal conjugation. We use cell-free synthetic biology to design and produce universal influenza vaccine and genome-free virus-like particle for human health applications. The resulting trimeric influenza hemagglutinin stem domain could be used as a potentially broadly protective influenza vaccine. The virus-like particle is extensively modified to improve its functional properties for better vaccine design, drug delivery, and cancer therapy.

 

Yuan Lu received his B.S. (2004) and PhD (2009) in Chemical Engineering from Tsinghua University, China. He was a postdoc in the Department of Biology at Johns Hopkins University, USA, from 2009 to 2010. In the following four years (2010-2014), he was a postdoc in the Department of Chemical Engineering at Stanford University, USA. Currently he is a project researcher at the University of Tokyo, Japan.