茎-环-链结构DNA适配体广谱中和蓖麻毒素和相思豆毒素

Abstract

Ricin and abrin are classified as Type II ribosome-inactivating proteins (RIPs) toxins, posing significant potential threats to public safety and in bioterrorism incidents. They exert catalytic N -glycosidase activity by specifically recognizing highly conserved structural domains within the α-sarcin/ricin loop (SRL) of ribosomal rRNA, consequently inhibiting protein synthesis and ultimately inducing cell death. Currently, no licensed drugs are available for Type II RIPs, making the development of antidotes with broad-spectrum activity highly imperative. In this study, we engineered a series of DNA aptamers featuring “stem-loop-chain” structures, designed to mimic the natural substrate, enabling spectrum inhibition of ricin and abrin toxins. Results indicated that most aptamers effectively inhibited the activities of ricin and abrin in both molecular and cellular screening models. The optimal aptamer, C-1, was demonstrated to be efficiently internalized into cells and had high-affinity binding to both toxins. In the cell poisoning protection assays, C-1 exhibited activity with IC 50 values of 80.2 ± 26.8 nM against ricin and 282.8 ± 19.5 nM against abrin. In the ICR mouse model, the survival rate of C-1 group was significantly higher than that of the control group. This work provides novel aptamer-based lead compounds with potential broad-spectrum inhibitory activity and establishes a technical framework for developing therapeutics against other biological toxins.