# Development and characterization of engineered therapeutic antibodies against SARS-CoV-2

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $393,750

## Abstract

PROJECT SUMMARY/ABSTRACT
The cell-to-cell spread of pathogenic tau between neurons is a devastating hallmark of Alzheimer’s disease (AD)
and other dementias. Recent evidence indicates that the neuronal receptor low-density lipoprotein receptor-
related protein 1 (LRP1) is the critical receptor required for endocytosis of pathogenic tau, suggesting the
blocking of LRP1-tau interactions as a therapeutic route. However, to achieve this requires comprehensive
atomic-level characterization of LRP1-tau engagement, as well as the identification of potent molecular inhibitors
and characterization of their mechanism of action. Work in the supplement, in response to NOT-AG-21-018
entitled “Alzheimer’s-Focused Administrative Supplements for NIH Grants that are Not Focused on Alzheimer’s
Disease” directly addresses key gaps in treatment of Alzheimer’s Disease in the context of blocking pathogenic-
tau. We demonstrate that LRP1 directly engages tau, which we will block with our recently discovered Rift Valley
Fever Virus glycoprotein N (RVFV Gn) that also directly binds LRP1. Using protein engineering, we will build
multivalent tau inhibitors, test their efficacy in tau binding and spreading, and evaluate the impact in a mouse
model. We will test the significance of Lrp1 in mouse models of AD. Altogether, this work will provide the
framework needed to develop potential viral glycoprotein-based therapies to prevent the spread of pathogenic
tau, addressing an urgent unmet need.

## Key facts

- **NIH application ID:** 10499269
- **Project number:** 3R01AI161374-02S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Gaya K. Amarasinghe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $393,750
- **Award type:** 3
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499269

## Citation

> US National Institutes of Health, RePORTER application 10499269, Development and characterization of engineered therapeutic antibodies against SARS-CoV-2 (3R01AI161374-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499269. Licensed CC0.

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