# A Gene Drive Therapy for HIV: Single-Administration Intervention for High-RiskGroups

> **NIH NIH DP1** · AUTONOMOUS THERAPEUTICS, INC. · 2024 · $716,839

## Abstract

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Project Summary
 Epidemiologists have long recognized the immense potential of targeting high-risk ‘core groups’ and
‘superspreaders’ to efficiently control infectious diseases. For HIV/AIDS, high-risk behaviors, such as in persons
who inject drugs (PWID) and female sex workers, establish core groups of superspreaders that drive disease
spread, exemplified by the HIV outbreak among PWID in Scott County, Indiana (Peters et al. NEJM 2016;
Campbell et al. JID 2017). Failure to target disease-control measures to these groups substantially weakens
the ability to contain HIV outbreaks and reduce incidence (UNAIDS Global AIDS Update, 2019). Unfortunately,
despite tremendous potential benefits, targeting disease-control measures to these high-risk groups is often not
feasible in practice due to the high cost and effort of reaching them (Maxmen Nature, 2018).
 To reach these key populations, this project will capitalize on gene drive technologies (National
Academy of Sciences, 2016 report). Gene drives are synthetic constructs engineered to expand within key
populations, genetically displace the pathogen, and thereby control disease spread. Modern gene drives—
based upon Cas9—are currently in field trials to control malaria in Burkina Faso, Brazil, and other locations. The
rationale for an HIV gene drive is based upon our extensive preliminary studies showing that prototype HIV gene
drives have demonstrated efficacy in humanized mice and could constitute single-administration interventions
with a high barrier to resistance (Tanner et al, Nature, in review). Epidemiological analyses indicate that gene
drives would spread through high-risk HIV-infected groups via the same risk factors as HIV. In particular, for
injection drug use in PWID—when multiple HIV variants co-transmit—gene-drive platforms would be uniquely
suited to overcome existing targeting obstacles and reach precisely those hardest-to-reach superspreaders.
 This proposal will test a prototype gene drive for HIV. First, prototype gene drives will be tested in patient
cells from PWID to validate preliminary in vitro efficacy in primary cells and humanized mice. Second,
established non-human primate (NHP) models of HIV infection will be used to assay safety (immunogenicity and
genotoxicity), efficacy, and the potential of gene drives to expand and transmit within HIV-infected PWID
populations using an injection drug use animal-to-animal transmission model in NHPs. Finally, based on our
positive humanized-mouse data and existing clinical trial precedents (e.g., NCT03617198, a 24-week ATI trial
that was approved based on humanized-mouse data) we will initiate an early Phase-I/0 clinical intervention trial
in an end-of-life HIV cohort (Last Gift cohort, a drug-use population). This trial will test safety and efficacy of the
HIV gene drive in lowering set-point viremia. Overall, these studies will propel development of gene drive
technologies to target high-risk PWID populations. Ultimately, HIV gen...

## Key facts

- **NIH application ID:** 11214723
- **Project number:** 7DP1DA051144-06
- **Recipient organization:** AUTONOMOUS THERAPEUTICS, INC.
- **Principal Investigator:** Leor S Weinberger
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $716,839
- **Award type:** 7
- **Project period:** 2020-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11214723

## Citation

> US National Institutes of Health, RePORTER application 11214723, A Gene Drive Therapy for HIV: Single-Administration Intervention for High-RiskGroups (7DP1DA051144-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11214723. Licensed CC0.

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