In Vivo MicroRNA-Based Inhibition of Experimental Cestode Infection.

Abstract

Cestodes (class Cestoda) include zoonotic parasites such asspp. andspp., which cause significant morbidity and mortality in endemic regions, particularly among pastoral and rural populations in low-, upper-, and middle-income countries. Their developmental plasticity reflects finely tuned regulatory mechanisms controlling gene expression throughout complex life cycles and infection stages. Despite expanding genomic resources, functional postgenomic studies remain scarce. MicroRNAs (miRNAs) are critical regulators of gene expression, influencing diverse developmental and physiological processes. Among them, miR-71-5p is highly expressed in cestodes, absent in vertebrates, and predicted to regulate essential parasite genes. Here, we employed a chemically modified antisense oligonucleotide to assess the impact of miR-71-5p knockdown duringinfection. To the best of our knowledge, this represents the firstreport of miRNA knockdown in a cestode infection model. Treated mice exhibited a 67% (3-fold) reduction in parasitic mass compared with controls, suggesting that miR-71-5p is essential for infection establishment and progression. Toxicity analyses in uninfected mice revealed no adverse effects. Whole-mounthybridization showed broad miR-71-5p expression across tissues, including germinative cells, suggesting a pleiotropic role. These findings advance the understanding of miRNA-mediated regulation in cestodes and highlight these small RNAs as promising therapeutic targets for neglected tropical diseases (NTDs) prioritized by the World Health Organization (WHO).