# RNA encoded nanobody-based immunotherapeutics targeting essential, host-interactive schistosome ectoenzymes

> **NIH NIH R21** · TUFTS UNIVERSITY BOSTON · 2024 · $206,250

## Abstract

Schistosomes are parasitic flatworms that cause a chronic, debilitating disease afflicting
>200 million people in >70 countries. Since there are limited anti-schistosome drugs
available and since these is no vaccine to prevent infection, we aim here to generate and
test nanobody-based immunotherapeutics targeting essential surface-exposed parasite
proteins as a novel intervention to control schistosomiasis. Nanobodies (camelid single-
domain antibodies or VHHs) are small, versatile binding agents that can be multimerized
for enhanced activities and delivered effectively by formulated mRNA. We have identified
and characterized three S. mansoni tegumental ectoenzymes (SmNPP5, SmT-AChE,
SmCA) that represent novel molecular targets for intervention to treat schistosomiasis.
Each of the three enzymes is exposed at the host parasite interface and each is essential
for the parasite to infect its vertebrate host. We aim to generate nanobodies that inhibit the
function of these three target enzymes (each enzyme has been purified in functional form
in CHO-S cells). The small size, stability to heat and pH extremes, low immunogenicity,
and facility to express as multimers with enhanced activities, makes VHHs preferred
therapeutic agents. We exploit advances in RNA therapeutics as our strategy to efficiently
and economically deliver sustained levels of serum VHH-based therapeutics. Our overall
goal is to generate a simple, practical, and potent anti-schistosome therapeutic that
curtails disease at all stages of infection. In sum, we have identified new, well
characterized, accessible and rational targets for anti-schistosome intervention, and
we incorporate an innovative, novel, cutting-edge approach to control
schistosomiasis. We have assembled a strong team and have on-hand all reagents and
tools necessary to ensure the success of this project. Our data will act as a proof of
principle supporting an approach that, in the longer term, could form the basis of a new
therapeutic for human schistosomiasis, as well as for other debilitating helminth diseases.

## Key facts

- **NIH application ID:** 10747442
- **Project number:** 5R21AI173458-02
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Charles Bix Shoemaker
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $206,250
- **Award type:** 5
- **Project period:** 2022-12-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747442

## Citation

> US National Institutes of Health, RePORTER application 10747442, RNA encoded nanobody-based immunotherapeutics targeting essential, host-interactive schistosome ectoenzymes (5R21AI173458-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10747442. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*