Synthetic Virology: Development of gene delivery vectors/synthetic vaccines

There is worldwide interest in exploiting our modern understanding of genomics to target gene expression therapeutically via a variety of mechanisms, such as transgene insertion and CRISPR-Cas gene editing. Such approaches require the transport of large genetic cargoes across cell membranes. Laboratory protocols for this transport are not easily transposed to the clinic. Natural viruses accomplish precisely this task by delivering their genomes with significant cell tropism to new host cells. We are repurposing such natural delivery systems to deliver nucleic acid cargoes, primarily RNAs to cells using picornaviruses and alphavirus capsid proteins and information on the multiple RNA packaging signals within their genomes. Production of non-infectious, bespoke virus-like particles (VLPs) is also being used to present stable, neutralising epitopes as the basis of a synthetic vaccine.

Techniques uesd include: gene cloning; synthetic gene construction; cell culture; viral infection assays; VLP purification; electron microscopy; ultracentrifugation; single molecule spectroscopy