# Evolving Novel AAV Vectors for Gene Therapy to Cure HIV

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $985,350

## Abstract

PROJECT SUMMARY
With the most people ever in history currently living with HIV, stopping the HIV epidemic remains imperative.
Combination antiretroviral therapy (ART) limits viral replication, but is not curative. Thus, there is an urgent need
to design a functional cure via elimination of the viral reservoir. Timothy Brown, aka the Berlin Patient, and Adam
Castillejo, aka the London patient, were cured of HIV following leukemia-related, MHC-matched, allogeneic
hematopoietic stem cell transplantation (HSCT) from a CCR5-deficient donor. While a CCR5-deficient immune
system can demonstrably yield a functional HIV cure, allogeneic stem cell transplantation is not scalable to the
general population and alternate approaches are needed. We have demonstrated that the CCR5-specific
antibody Leronlimab can pharmacologically mimic a CCR5 deficient donor by occupying all available CCR5
molecules. In order to deliver Leronlimab as a gene therapy option, new delivery modalities are needed. Here,
we are proposing to utilize our novel directed evolution technique to generate AAV vectors specific for T and B
cells. These novel AAV vectors will facilitate in vivo delivery of Leronlimab expression here, but more importantly
will support the future use of other anti-HIV approaches including CRISPR-Cas9, chimeric antigen receptors,
and broadly neutralizing antibodies by delivering these therapeutics to the relevant immune cell type. In specific
aim 1, we will generate and characterize AAV bearing capsids that target T and B cells specifically across both
macaques and humans. In aim 2, we will demonstrate proof-of-concept utility of these new AAVs by delivering
Leronlimab to SHIV-infected, ART suppressed macaques to determine if a functional cure can be achieved with
this approach. This work would expand our knowledge of the mechanism of HIV cure by showing the utility of
long-term antibody-based competitive CCR5 inhibition and establish a new set of AAV vectors to support in vivo
delivery of anti-HIV therapeutics.

## Key facts

- **NIH application ID:** 10371617
- **Project number:** 1R01AI166969-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Aravind Asokan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $985,350
- **Award type:** 1
- **Project period:** 2022-06-07 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371617

## Citation

> US National Institutes of Health, RePORTER application 10371617, Evolving Novel AAV Vectors for Gene Therapy to Cure HIV (1R01AI166969-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371617. Licensed CC0.

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