This grant supports experiments to assess whether “xenobiotic nucleic acids” (XNAs)—DNA/RNA-like polymers not found in nature—could serve as alternative carriers of genetic information, with implications for understanding possible early-life chemistries and for building simplified synthetic cells. A team led by Lijun Zhou at the University of Pennsylvania will use Sloan funding to characterize how efficiently and how accurately a specific class of XNA polymers (NP-DNA and NP-RNA) can be copied from a template without the use of enzymes. The work will measure copying speed and error rates across a diverse range of XNA sequences and varying environmental conditions (such as pH, temperature, and ion concentrations). The team will also investigate how the addition of reactivity-enhancing biomolecules affects copying speed and fidelity and whether and how genetic information could be transferred between the two types of polymers. In addition, the project team will run laboratory evolution experiments to determine whether these XNAs can undergo Darwinian evolution to expand their functionality, focusing on evolving XNA sequences that can catalyze useful reactions, such as joining short XNA strands together.