Unmodified RNA sequences form unusual stable G-quadruplexes with potential anti-RSV and anti-angiogenesis applications.

DNA or RNA sequences with customizable designs form unique three-dimensional structures that bind to targets with high precision and strength, making them promising tools for medical diagnosis and therapy. However, their clinical use is limited by rapid clearance from blood and safety concerns. This study introduces a novel RNA-based structure called G-quadruplex, which requires no chemical modifications. These G-quadruplexes remain highly stable in biological fluids, retaining over 90% of their concentration after 96 h. Experiments confirm their strong binding to a cell surface protein (nucleolin) without significant cellular uptake, resulting in nearly zero harm to cells. They effectively block respiratory syncytial virus infection, suppress the growth and movement of human blood vessel cells, and prevent new blood vessel formation in chicken embryos, even without specialized delivery systems. These stable G-quadruplex structures demonstrate dual potential for treating cancers and viral infections, offering a versatile and safe strategy for future therapies.