Antibody targeting the anti-parallel topology of human telomeric G-quadruplex DNA

G-quadruplexes (G4s) are four-stranded nucleic acid structures that have gathered a significant attention due to their involvement in key biological processes, including gene regulation, genome stability, and telomeres maintenance. Some G4 antibodies have been developed to selectively recognize these structures over duplex DNA; however, most, even the widely studied BG4 and 1H6, bind G4s in a general manner and lack discrimination between distinct topologies, particularly between parallel and antiparallel conformations. In this study, we report on the development and characterization of a novel antibody selected via phage display method using a constrained antiparallel G4 structure mimicking one of the conformation adopted in vitro by the human telomeric sequence. Our findings demonstrate that this new antibody selectively recognizes the antiparallel topology of the telomeric G4 sequence, a property further validated in cellular models.