# A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups

> **NIH NIH DP1** · J. DAVID GLADSTONE INSTITUTES · 2021 · $189,000

## Abstract

ABSTRACT
Substantial evidence now indicates that HIV-infected individuals are at a significantly elevated risk for severe
COVID-19 disease when infected with SARS-CoV-2. Moreover, persons who use and inject drugs (PWUD and
PWID) have a high-risk of HIV infection and exposure to SARS-CoV-2 and face major barriers to accessing
antiviral therapies (i.e., are often immunocompromised). The problem is further exacerbated by the emergence
of SARS-CoV-2 variants that escape vaccine-mediated immunity—it is now evident that immunocompromised
individuals promote the evolution of SARS-CoV-2 escape variants and HIV-infected PWUD/PWID with barriers
to treatment represent such a population. Consequently, there is a critical unmet medical need for new
therapeutics that could treat HIV as well as SARS-CoV-2—particularly the emerging variants of concern’—and
could be effectively deployed in difficult-to-reach, high-risk populations (e.g., PWUD/PWID). The long-term goal
of this work is to develop single-administration therapies for HIV-1 and SARS-CoV-2 variants to effectively reach
PWID/PWUD populations. The specific objective of this supplement proposal is to test efficacy of our recently
developed Gene Drive Therapies (GDT) against HIV and SARS-CoV-2 variants in patient cells from HIV+ PWID.
This effort will build heavily off our recent success in engineering GDTs for HIV-1 (see Parent Award) and Zika
Virus (ZIKV), as well as our extensive preliminary in vitro data showing efficacy of GDTs against SARS-CoV-2
variants. The central hypothesis—based on our extensive preliminary in vitro studies—is that our engineered
GDT candidates will have the capacity to reduce both SARS-CoV-2 viral load and pathogenesis, including of
SARS-CoV-2 variants of concern, and HIV viral load, thereby serving as a single-administration, combination
therapeutic for HIV-1 and SARS-CoV-2. The rationale for a GDT for SARS-CoV-2 is based on our preliminary
data showing that GDTs significantly reduce SARS-CoV-2 replication in cell culture, are equally effective against
CoV-2 variants and from extensive studies on HIV-1 in humanized mice and positive FDA meetings. We will
achieve our objectives via two specific aims: (i) Quantify in vivo efficacy of the recently developed GDT in
reducing SARS-CoV-2 viral replication and pathogenesis in hamsters; and (ii) Develop a lung-organoid co-
culture to test efficacy of GDTs against HIV-1 and SARS-CoV-2 in patient-derived cells from HIV+ PWIDs. While
the GDT approach carries inherent risks, single-administration therapeutics active against both SARS-CoV-2
variants and HIV would be highly beneficial, particularly for treating difficult-to-reach, high-risk PWID populations.
The studies proposed here will also have broad fundamental significance by establishing a novel culture model
and tool to assay how SARS-CoV-2 and HIV infections interact in the PWUD/PWID setting (i.e., in the context
of Substance Use Disorders (SUDs) in at-risk populations) and will pro...

## Key facts

- **NIH application ID:** 10381365
- **Project number:** 3DP1DA051144-02S1
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Leor S Weinberger
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $189,000
- **Award type:** 3
- **Project period:** 2020-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10381365

## Citation

> US National Institutes of Health, RePORTER application 10381365, A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups (3DP1DA051144-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10381365. Licensed CC0.

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