# Next-generation extracellular vesicle biologics to target central nervous system and peripheral reservoirs of HIV

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $805,578

## Abstract

Abstract
In the era of combined antiretroviral therapy (cART), mortality and morbidity associated with HIV-1
infection has been reduced. Nevertheless, a wide range of AIDS-related conditions as well as serious
non-AIDS events (SNAEs) continue to afflict people living with HIV (PLWH). Improved long-term
strategies are needed, ranging from easier administration to better suppression to functional cure.
Barriers to functional cure include a limited ability to deliver activators and other bioactive molecules
into tissue reservoirs of HIV, particularly the possible reservoirs in the central nervous system (CNS).
Representing a novel mode of delivery, extracellular vesicles (EVs) are double membrane-bound
particles, released by all known cell types, that engage in intercellular communication by shuttling
components of the parent cell (such as proteins and RNAs) to target cells. EVs contribute to disease
pathogenesis and are actively investigated, especially in cancers, as biomarkers, actors in disease
processes, and potential therapeutics. Importantly, EVs have been shown to cross biological
barriers, even the blood-brain barrier, and can be easily delivered to the brain. EVs thus provide an
exceptional opportunity to deliver components of HIV control or reactivation/cure to tissue reservoirs,
with potential for cell-specificity.
 To this end, we have assembled a multidisciplinary team with two major, unique assets. The first is a
novel small EV-transcriptional activator (sEVTA) tool that has already passed in vitro and in vivo
tests. In this system, retroviral transactivator proteins are specifically packaged into EVs, which can
be further functionalized with tracers and surface peptides for cell targeting. The second is our well
established SIV/macaque model, which has been used successfully to study retroviral latency,
rebound, and retrovirus-associated CNS disease. We will conduct careful nonhuman primate dosing
and distribution studies followed by optimized intravenous and intranasal delivery of sEVTAs. Effects
of sEVTAs on viral rebound will be assessed with innovative tools in circulating and peripheral tissue
reservoirs (Aim 1), followed by reservoirs in the CNS (Aim 2). In Aim 3, we will investigate the
potential toxicity of these approaches, with particular focus on the central nervous system, and
explore more cell-targeted approaches.
 The goal of these studies is to use sEVTAs to reactivate latent retroviruses in the CNS and the
periphery. However, the project will also provide much-needed information about EV delivery,
distribution, and efficacy in primates that can be harnessed in development of a variety of therapies
for HIV infection and disease.

## Key facts

- **NIH application ID:** 9884730
- **Project number:** 5R01AI144997-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Bharat Ramratnam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $805,578
- **Award type:** 5
- **Project period:** 2019-03-05 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884730

## Citation

> US National Institutes of Health, RePORTER application 9884730, Next-generation extracellular vesicle biologics to target central nervous system and peripheral reservoirs of HIV (5R01AI144997-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9884730. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*