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

> **NIH NIH DP1** · J. DAVID GLADSTONE INSTITUTES · 2020 · $189,000

## Abstract

PROJECT SUMMARY/ABSTRACT
For COVID-19, persons who inject drugs (PWID) have been identified as a population at high-risk of exposure
to SARS-CoV-2 (the virus that causes COVID-19) because of their increased risk of homelessness or
incarceration—situations linked to increased rates of the disease transmission and co-infection with HIV-1.
Given that a SARS-CoV-2 vaccine is likely 12–24 months away, there is a critical unmet medical need for medical
countermeasures that could contain COVID-19 outbreaks in the general population and in these difficult-to-reach
high-risk populations such as PWIDs in particular. Moreover, there is a fundamental gap in our understanding
of SARS-CoV-2 infection and pathogenesis in these at-risk PWID populations. Evidence indicates that SARS-
CoV-2 infects and depletes T lymphocytes and many HIV-infected PWID have limited access to antiretroviral
therapy and consequently exhibit pre-existing CD4+ T-cell depletion. Hence, SARS-CoV-2 infection could
accelerate clinical progression to AIDS, or alternatively, SARS-CoV-2 infection in HIV+ PWID could exacerbate
COVID-19 clinical symptoms leading to elevated risk of death. Thus, HIV+ PWID may be at elevated risk of
death from SARS-CoV-2 infection. In these PWID populations, reducing T-cell depletion would be highly
beneficial to halting clinical progression and may a viable long-term therapeutic goal. The specific objective of
this supplement proposal is to repurpose existing technologies to rapidly develop a Gene Drive Therapy (GDT)
candidate for SARS-CoV-2 and quantify its breadth of interference and transmission in vitro in patient T-cells
from HIV+ PWID. This effort will build heavily off our recent success in engineering an HIV-1 GDT (see Parent
Award) and a GDT against Zika Virus (ZIKV), demonstrating that the GDT concept can be repurposed for other
viruses. The central hypothesis—based on extensive preliminary studies in HIV and ZIKV—is that a putative
SARS-CoV-2 GDT, depleted of all the pathogenic viral genes, could target the same cells as wild-type SARS
CoV-2 (including T lymphocytes), compete for intracellular resources, and reduce SARS CoV-2 viral load and
pathogenesis, thereby serving as a single-administration therapeutic. The rationale for a GDT countermeasure
for SARS CoV-2 is based on extensive data for HIV-1 in humanized mice and positive FDA meetings. We will
achieve our objectives via two specific aims: (i) Engineer a SARS-CoV-2 GDT candidate (by adapting the existing
Bioreactor platform); and (ii) Test the SARS CoV-2 GDT candidate's protective effect on patient T-cells from an
HIV+ PWID cohort in Tijuana Mexico. While the GDT approach carries inherent risks, single-administration
therapeutics would be highly beneficial particularly for treating difficult-to-reach, high-risk PWID populations.
Regardless of the success of GDTs in protecting against T-cell depletion, the studies proposed here will have
broad fundamental significance by assaying how SARS-CoV-2 i...

## Key facts

- **NIH application ID:** 10163412
- **Project number:** 3DP1DA051144-01S1
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Leor S Weinberger
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **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/10163412

## Citation

> US National Institutes of Health, RePORTER application 10163412, A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups (3DP1DA051144-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10163412. Licensed CC0.

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