Oral Presentation Royal Australian Chemical Institute National Congress 2026

Novel DNA-targeting approaches to advance treatment of infectious diseases (140457)

Ludovica Monti 1 , Genta Firth 1 , Joana Correia Faria 2 , John Kelly 3 , Gem Flint 4 , Silvia Galli 4 , Thomas Maher 4 , Lingxiao Long 1 , John Karas 5 , Fazel Shabanpoor 6 , Marco Di Antonio 4
  1. School of Chemistry and The Bio21 Institute, The University of Melbourne, Melbourne, Victoria, Australia
  2. Department of Biology and York Biomedical Research Institute, University of York, Heslington, York, UK
  3. Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK
  4. Department of Chemistry, Imperial College London, London, UK
  5. School of Chemistry, The University of Melbourne, Melbourne, Victoria, Australia
  6. Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia

Parasitic pathogens responsible for neglected tropical diseases continue to disproportionally affect populations facing economic hardship, resulting in high rates of morbidity and mortality. Current treatments are limited and often associated with severe adverse effects; moreover, the risk of emergence of drug resistance remains a concern. There is, therefore, the need to develop new alternative strategies for therapeutic intervention.

Here, we present how DNA-targeting approaches integrated with genomic analyses enabled the identification of new druggable targets in these pathogens. In our recent work, we performed genome-wide mapping of DNA secondary structures, G-quadruplexes (G4s), across the genome of Trypanosoma parasites and interrogated their roles in gene expression and pathogen biology using combined bioinformatics, genomics, and transcriptomics approaches. Our findings demonstrate the functional relevance of G4s in parasite genomes and establish these structures as tractable molecular targets. This work provides a foundation for the development of chemical strategies targeting DNA secondary structures, opening new avenues for drug discovery and therapeutic innovation in infectious diseases.