Currently, there is an increasing amount of evidence indicating that exosomes and the
miRNAs they contain are crucial players in various biological processes. However, the role of exosomes and
miRNAs in
snake venom during the envenomation process remains largely unknown. In this study, fresh
venom from Naja atra of different ages (2-month-old, 1-year-old, and 5-year-old) was collected, and exosomes were isolated through ultracentrifugation. The study found that exosomes with inactivated
proteins and
enzymes can still cause symptoms similar to cobra envenomation, indicating that substances other than
proteins and
enzymes in exosomes may also play an essential role in cobra envenomation. Furthermore, the expression profiles of isolated exosome
miRNAs were analyzed. The study showed that a large number of
miRNAs were co-expressed and abundant in
cobra venom exosomes (CV-exosomes) of different ages, including miR-2904, which had high expression abundance and specific sequences. The specific miR-2094 derived from CV-exosomes (CV-exo-miR-2904) was overexpressed both in vitro and in vivo. As a result, CV-exo-miR-2904 induced symptoms similar to cobra envenomation in mice and caused liver damage, demonstrating that it plays a crucial role in cobra envenomation. These results reveal that CV-exosomes and the
miRNAs they contain play a significant regulatory role in cobra envenomation. Our findings provide new insights for the treatment of cobra
bites and the development of
snake venom-based medicines.