# Viral gene drive as a novel curative therapy for HSV infection

> **NIH NIH R21** · FRED HUTCHINSON CANCER CENTER · 2024 · $227,635

## Abstract

PROJECT SUMMARY/ABSTRACT
Herpesviruses such as Herpes simplex virus (HSV) 1 and 2 are ubiquitous DNA viruses that establish lifelong
infections. After primary infection, they enter latency and occasionally reactivate, causing recurrent disease.
HSV 1 and 2 establish latency in neurons, and reactivation causes lesions of the facial or genital area. HSV-1
and 2 lack vaccines or curative treatments and new therapeutic strategies against chronic HSV diseases are
critically needed. During an infection, cells are frequently co-infected by multiple virions, and therapeutic
approaches that rely on viral co-infection have great potential. We recently invented a CRISPR-based “viral
gene drive” that relies on viral co-infection to replace wild-type viruses with an engineered version. Our
strategy was inspired by similar methods developed in insects and uses CRISPR-Cas9 and homologous
recombination to efficiently propagate a genetic modification in the viral population, ultimately reducing viral
levels. Our discovery uncovered a new way to engineer herpesviruses for therapeutic and research purposes.
Our long-term goal is to design gene drives that could be used as curative therapies for HSV infection. Patients
suffering from chronic HSV disease could be treated with an engineered virus that recombines with wild-type
viruses in the latent reservoir and prevents viral outbreaks. In this innovative application, we propose to
determine if a viral gene drive can spread to the latent reservoir and inactivate wild-type viruses in mice latently
infected with HSV-1. In specific aim 1, we will use mouse models of HSV-1 infection to test if a gene drive can
suppress viral shedding in mice persistently infected with wild-type HSV-1. This will establish the potential of
gene drives to cure chronic HSV-1 infection. In specific aim 2, we will use fluorescently-labeled viruses and
mathematical modeling to quantify co-infection frequency during gene drive propagation in vivo. The rationale
is that gene drives rely on co-infection, and that a better understanding of the biology of co-infection is needed
for the development of our innovative therapeutic strategy. We will determine how often a gene drive reaches
latently infected neurons and establish if a gene drive can efficiently inactivate the latent reservoir. Altogether,
this project will test the therapeutic potential of a breakthrough technology and may lead to novel therapies that
significantly improve human health.

## Key facts

- **NIH application ID:** 10888848
- **Project number:** 1R21AI178255-01A1
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Marius Walter
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $227,635
- **Award type:** 1
- **Project period:** 2024-02-21 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888848

## Citation

> US National Institutes of Health, RePORTER application 10888848, Viral gene drive as a novel curative therapy for HSV infection (1R21AI178255-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10888848. Licensed CC0.

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