# Rational Structure-Based Design of Broad Neutralizing Humanized svMP mAbs

> **NIH NIH R21** · TEXAS A&M UNIVERSITY-KINGSVILLE · 2022 · $183,948

## Abstract

PROJECT SUMMARY
In this R21 award, we aim to develop a novel and broad neutralizing human monoclonal antibody for treating
snakebite envenoming by rational structure-based design in order to produce a more effective and safer next
generation antivenom.
Snake envenomation is a serious global public health concern and ranked on the Wor
ld
Health Organization’s list of neglected tropical diseases,
killing on average 125,000 people per year and
leaving another 400,000 permanently disabled. The majority of snake envenomation in the US, inflicted by
members of the snake family Viperidae, causes local tissue damage (such as myonecrosis, blisters, and local
inflammation and pain) and systemic effects, including hemorrhage and coagulopathies which can lead to
shock, renal failure and death. Snake venom metalloproteinases are major causative agents for spontaneous
systemic bleeding and coagulopathies. Current antivenoms, produced by immunization of domestic animals,
have limited efficacy in the prevention of both local and systemic effects of Viperidae envenomation as well as
an associated risk of hypersensitivity reactions. Our long-term goal is to develop novel, effective humanized
antivenom therapeutics for Viperidae envenomation. The objective of this project is to test the hypothesis that
camelid-inspired inhibitory paratope synthetic human antibodies targeted to the active site of medically-relevant
viperid venom metalloproteinases (svMPs) can provide broad antivenom protection without cross-reaction with
human metalloproteinases and without the risk of hypersensitivity. This objective will be addressed through our
established collaboration of complementary expertise between the snake venom toxinology team at National
Natural Toxins Research Center (NNTRC) and the antibody discovery team at University of California
Riverside (UCR). To test our hypothesis, we will address the following three Specific Aims. Aim 1: Qualitative
and Quantitative Characterization of the hemorrhagic activity of viperid svMPs (Galan), Aim 2: Discovery of
Broadly Neutralizing svMP-Specific Human mAbs (Ge). Aim 3: Evaluation of the antivenom efficacy of svMP
inhibitory mAbs in vitro (Ge) and in vivo (Sanchez). The proposed research is significant because it will
advance our understanding of the hemorrhagic aspects caused by snake envenomation at biochemical/cellular
levels and develop effective humanized mAb antivenoms, which will be directly translatable for therapeutic use.
The novelties of our project are (1) development and application of a novel Hemorrhage Score system to
characterize svMPs; (2) isolation of humanized svMP-specific antivenom mAbs from libraries carrying novel
convex paratopes; (3) development groundbreaking functional (rather than binding-based) HTS for facile
discovery of mAbs inhibiting hemorrhagic snake toxins; and (4) potentially shifting the conventional antivenom
production into specific neutralizing humanized mAb therapeutics.

## Key facts

- **NIH application ID:** 10310508
- **Project number:** 5R21AI156156-02
- **Recipient organization:** TEXAS A&M UNIVERSITY-KINGSVILLE
- **Principal Investigator:** Xin Ge
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $183,948
- **Award type:** 5
- **Project period:** 2020-12-02 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10310508

## Citation

> US National Institutes of Health, RePORTER application 10310508, Rational Structure-Based Design of Broad Neutralizing Humanized svMP mAbs (5R21AI156156-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10310508. Licensed CC0.

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