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bioRxiv · 10.1101/2022.01.11.475978

RNA-based therapy for Cryptosporidium parvum infection: proof-of-concept studies

Castellanos-Gonzalez, A.·Sadiqova, A.·Ortega-Mendez, J.·White, A. C.
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Abstract

Cryptosporidium is a leading cause of moderate-to-severe diarrhea in children. Nitazoxanide, the only FDA-approved treatment for cryptosporidiosis, has limited efficacy in those at highest risk for sequelae. RNA-argonaute (Ago) complexes to Cryptosporidium nucleoside diphosphate kinase (cpNDK) decreased the Cryptosporidium parvum mRNA by 95% in infected cells in vitro. Treatment of mice by oral gavage with ssRNA/Ago complexes encapsulated in lipid nanoparticles led to delivery of the complexes into intestinal epithelial cells. Treatment of C. parvum infected mice with ssRNA/Ago complexes targeting cpNDK led to the resolution of oocyst shedding in 4/5 SCID/beige mice. These results confirm the potential use of antisense therapy as an alternative approach to cryptosporidiosis treatment.

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Castellanos-Gonzalez, A., Sadiqova, A., Ortega-Mendez, J., White, A. C.. 2022-01-12. RNA-based therapy for Cryptosporidium parvum infection: proof-of-concept studies. https://doi.org/10.1101/2022.01.11.475978

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