# Biology and Engineering of Botulinum Neurotoxins.

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $541,670

## Abstract

Project Summary
Botulinum neurotoxins (BoNTs) are a family of bacterial protein toxins. They are one of the six
most dangerous potential bioterrorism agents. Members of BoNTs, BoNT/A (Botox) and BoNT/B,
are also FDA-approved for treating a growing list of disorders, as well as for reducing wrinkles.
Understanding the molecular mechanisms for this family of toxins, engineering toxins to improve
their therapeutic uses, and developing effective countermeasures have been the focus of our lab.
Our prior funding cycle has led to major discoveries in understanding toxin receptors, identification
of novel BoNT-like toxins, and development of new treatment that can neutralize BoNTs inside
motor neurons. In this renewal proposal, we will address both side of BoNTs through protein
engineering approaches: Aim 1 seeks to develop a novel chimeric toxin that can preferentially
bind to the toxin receptor isoform dominantly expressed in autonomic and sensory neurons and
evaluate its improvement over the standard Botox for treating overactive bladder conditions in
rodent models. Aim 2 seeks to develop and evaluate novel nanobody-based triple-epitopic
antibodies (NTAb) for neutralizing and clearing BoNTs in the circulatory system. NTAb is
constructed by fusion of three nanobodies targeting distinct regions on BoNTs and then to a Fc,
thus generating an artificial antibody that can achieve binding of three NTAb to a single toxin
molecule, which promotes toxin clearance. In this proposal, we will develop two sets of NTAb,
targeting two most common toxins, BoNT/A and BoNT/B, respectively, and thoroughly evaluate
their efficacy, pharmacokinetics, and toxin clearance using rodent and guinea pig models.

## Key facts

- **NIH application ID:** 10980668
- **Project number:** 2R01NS080833-12
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Min Dong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $541,670
- **Award type:** 2
- **Project period:** 2013-03-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980668

## Citation

> US National Institutes of Health, RePORTER application 10980668, Biology and Engineering of Botulinum Neurotoxins. (2R01NS080833-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10980668. Licensed CC0.

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