# Exosome based intraocular therapy combined with active targeting of ocular neovascularization

> **NIH NIH R56** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $417,431

## Abstract

Abstract
Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent monotherapy is the current mainstay
for treating neovascular age-related macular degeneration (NVAMD). However, despite its vision saving benefit,
some patients fail to respond to the treatment because of insufficient therapeutic effect and/or the socioeconomic
burden of frequently required repeat injection. Therefore, the long-term goal of our studies is to develop superior
or adjunctive approaches to the current anti-VEGF therapy that can provide active targeting of NVAMD, have
the capacity to deliver multiple drugs, and maintain long-term efficacy. Exosomes are naturally occurring, cell-
secreted, and nano-sized extracellular vesicles capable of carrying various cargos including microRNAs, proteins,
and lipids for cell-to-cell communications. Based on these characteristics, exosomes have great potential to be
used as novel carriers for intraocular drug delivery. Recently, we have shown that ASL-exosomes composed of
Anchor, Spacer, and Arg-Gly-Asp acid (RGD) Ligand-modification actively target angiogenesis in cancer.
However, studies demonstrating the utility of exosomes in intraocular drug delivery systems remains to be
explored. The overall objectives of this application are to develop a novel ASL-exosome based intraocular drug
delivery system for the treatment of NVAMD that actively targets ocular neovascularization (NV) and can deliver
multiple drugs with sustained efficacy. The central hypothesis of the proposal is that ASL-exosomes can co-
deliver Eylea and miR-24, a new intracellular target for choroidal NV, and effectively suppress NV by active
targeting and sustained drug delivery with minimal immune responses. We hypothesize that localized delivery
of ASL-exosomes to NV lesions using RGD-integrin ligand binding mediated active targeting will also increase
intracellular uptake of ASL-exosomes by integrin receptor-mediated intracellular endocytosis. The central
hypothesis will be tested by pursuing two specific aims. Aim 1 is to determine the mechanism by which ASL-
exosomes actively target ocular NV and to evaluate whether RGD mediated active intracellular uptake of ASL-
exosomes bypasses ocular cell tropism directed intracellular uptake of exosomes. Aim 2 is to determine
sustained multi-drug delivery using ASL-exosomes and related immune response. The research proposed in
this application is innovative, because the combination of an exosome-based intraocular drug delivery system
with active targeting is a novel strategy that has potential to change the current treatment paradigm from passive
targeting-directed monotherapy to active targeting-directed multi-drug delivery with sustained efficacy for the
treatment of various retinal and choroidal vascular diseases, such as NVAMD, diabetic retinopathy and retinal
vein occlusion.

## Key facts

- **NIH application ID:** 10690935
- **Project number:** 1R56EY034193-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Sun Young Lee
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $417,431
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690935

## Citation

> US National Institutes of Health, RePORTER application 10690935, Exosome based intraocular therapy combined with active targeting of ocular neovascularization (1R56EY034193-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10690935. Licensed CC0.

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