# Develop and evaluate efficacy of nanoformulated siBeclin1 delivered intranasally to eliminate HIV in brain

> **NIH NIH R21** · FLORIDA INTERNATIONAL UNIVERSITY · 2020 · $224,556

## Abstract

PROJECT SUMMARY
Develop and Evaluate the Efficacy of Nanoformulated siBeclin1 Delivered Intranasally to Eliminate HIV in the Brain.
The overall hypothesis is that small interfering (si) RNAs targeting the autophagy pathway can act as a synergistic
therapeutic agent with antiretroviral drugs to eliminate central nervous system (CNS) HIV reservoirs and viral associated
inflammatory responses in perivascular macrophages, microglia [1,2] and astrocytes [3]. To this end, we will synthesize a
siBeclin1 siRNA- polyethylenimine (PEI) polyplex [4] to facilitate intranasal delivery to the brain [4]. The
nanoformulated siBeclin1 which transiently diminishes expression of host protein Beclin1, will be tested for its efficacy in
eliminating brain cell HIV reservoirs in humanized mice. Efficient intranasal delivery (Figure 1), deployment of mannose
decorated particles (Figure 2) and quantitative measures of viral replication will be employed (Figure 3). In the first two
sub aims (a &b) of Aim 1, we will quantitatively measure the pharmacokinetics and bio-distribution of siBeclin1 in brain,
lung, heart, liver and kidney by reverse transcription polymerase chain reaction (RT-PCR) and liquid chromatography-
tandem mass spectrometry (LC-MS/MS) methodologies. Since cell toxicity is a problem encountered with many
antiretroviral therapies, in Aim 1c, morphological changes due to cytotoxicity in the brain will be assessed by histology
using Hematoxylin and eosin (H&E) and Nissl staining to detect for neuronal damages. Followed by
immunohistochemical labeling of neuronal nuclei (NeuN) or microtubule-associated protein 2 (MAP2) to assess for the
surviving neuronal cells in the brain. The cell marker, ionized calcium binding adaptor molecule 1 (Iba-1) or CD68
specific for microglia and glial fibrillary acidic protein (GFAP) specific for astrocytes will be used to detect Glial
activation (gliosis). Inflammatory responses will be measured by cytokine and chemokine membrane-based antibody
arrays and confirmed by colorimetric sandwich enzyme-linked immunosorbent assay (ELISA). Chemistry analysis on the
levels of blood urea nitrogen and alanine transaminase activity, will indicate toxicity of the kidneys and liver,
respectively. In Aim 2a, we will determine the efficacy of the nanoformulated siBeclin1 on the different aspects of CNS
pathology induced by HIV ± antiretroviral drugs including (1) viral replication (measured by PCR-based assays); (2)
secretion of immune responses (measured by ELISA-based assays); (3) glial activation and (4) neuronal health (measured
by histological and immunohistochemical based assays). Special emphasis will be placed on the hippocampus and the
basal ganglia as these regions are most affected by HIV disease and are critical for brain development, learning and
memory processes and sensory motor function. In aim 2b, behavioral changes elicited by HIV infection alone or in
combination with antiretroviral drug regimen ± nanoformulated siBeclin1 wil...

## Key facts

- **NIH application ID:** 9893032
- **Project number:** 5R21MH118985-02
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** NAZIRA EL-HAGE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $224,556
- **Award type:** 5
- **Project period:** 2019-03-13 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893032

## Citation

> US National Institutes of Health, RePORTER application 9893032, Develop and evaluate efficacy of nanoformulated siBeclin1 delivered intranasally to eliminate HIV in brain (5R21MH118985-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893032. Licensed CC0.

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