Genetic information storage in all biology relies exclusively on DNA and RNA. Nevertheless, DNA and RNA are not the only viable genetic materials available: a number of synthetic nucleic acids (XNAs) can fulfil that function and are accessible through the systematic engineering of nucleic acid processing enzymes. Our goal is to establish an XNA episome – a synthetic genetic element in XNA that can be stably maintained and replicated without any natural nucleic acid intermediates and compatible with in vivo systems.
Working with the well characterised Phi29 bacteriophage as a chassis, we are developing novel in vitro and ex vivo directed evolution methodologies to systematically engineer all components required for the maintenance and replication of an XNA episome compatible with in vivo systems.