# Development of a novel RNA interference method to reduce Cryptosporidium infection

> **NIH NIH R21** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $197,500

## Abstract

Project Summary/Abstract
The World Health Organization reports diarrhea kills around 760,000 children under five every year.
Cryptosporidium is a leading cause of diarrhea morbidity and mortality. Therefore novel treatments against this
pathogen are urgently needed. The limitations of tools used to genetically manipulate gene expression in this
parasite have been identified as a major hurdle for drug and vaccine development. To circumvent this gap, we
developed a rapid method to silence genes in this parasite using pre-assembled complexes (minimal RISC
complexes, ready to silence) of Cryptosporidium single-stranded RNA and the human enzyme Argonaute 2
(ssRNA/Ago). We used this method to determine the role of selected genes during Cryptosporidium infection.
We identified four genes (Actin, Nucleoside diphosphate kinase, Rhomboid protein 1 and transcription factor
Ap2) that block proliferation and egress of Cryptosporidium parasites. Therefore, we hypothesized that
ssRNA/Ago based therapy may be optimized in order to treat Cryptosporidium infection. In this project our goal
is to develop a method to block parasite proliferation on infected intestinal cells. Our specific aims are: 1)
Developing a novel method to reduce Cryptosporidium infection by silencing essential genes and to test the
silencing with ssRNA/Ago complexes under physiological conditions and 2) Demonstrate the feasibility to
deliver ssRNA-Ago complexes in the intestine. The characterization of these mechanisms will be essential to
explore the feasibility to use RNA interference technology as novel alternative for the treatment of
Crypotosporidiosis

## Key facts

- **NIH application ID:** 10112176
- **Project number:** 5R21AI151901-02
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Alejandro Castellanos-Gonzalez
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,500
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112176

## Citation

> US National Institutes of Health, RePORTER application 10112176, Development of a novel RNA interference method to reduce Cryptosporidium infection (5R21AI151901-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10112176. Licensed CC0.

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