# Targeted delivery of therapeutics into motor neurons for post-exposure treatment of botulism

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $583,280

## Abstract

Project Summary
 The family of bacterial toxins, botulinum neurotoxins (BoNTs), produced by spore-
forming Gram-positive Clostridium bacteria, are the most potent toxins known. They cause the
deadly paralytic disease botulism in humans and animals. These toxins are one of the six most
dangerous potential bioterrorism agents (Category A and Tier 1). They target motor neurons
with extreme specificity, enter the cytosol of neurons, and block neuronal activity, causing
muscle paralysis. A major contributor to the threat of BoNTs is their extremely long half-life
within the cytosol of motor neurons – the toxin resides in the cytosol for 4-6 months in humans
and causes persistent paralysis for months. To date, no therapeutics can inhibit toxins within the
cytosol of neurons.
 Here we propose to create an effective post-exposure treatment for this top-priority
bioterrorism agent and deadly bacterial toxins. This treatment is based on modifying a recently
discovered new bacterial toxin BoNT/X and utilizing this engineered protein to deliver a fused
neutralizing antibody against BoNTs into the cytosol of motor neurons. Our extensive
preliminary studies have provided working prototypes, which completely rescue mice from
systemic toxicity of BoNTs in multiple post-exposure models. Here we propose three aims to
further validate our hypothesis by (1) refining the chimeric toxin platform; (2) optimizing the
nanobody cargo against BoNTs; and (3) establishing pharmacokinetic parameters and
validating therapeutic efficacy in both rodent and guinea pig models.
 Success of these aims will create an effective post-exposure treatment for a top-priority
bioterrorism agent, and also develop a novel protein-based delivery platform for targeting motor
neurons, thus offering new tools for targeting cytosolic processes and “undruggable” proteins in
neurons.

## Key facts

- **NIH application ID:** 10210524
- **Project number:** 1R01NS117626-01A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Min Dong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $583,280
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210524

## Citation

> US National Institutes of Health, RePORTER application 10210524, Targeted delivery of therapeutics into motor neurons for post-exposure treatment of botulism (1R01NS117626-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10210524. Licensed CC0.

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