# Targeted Nano-enhanced Optical Delivery of opsin for dry-AMD therapy

> **NIH NIH R44** · NANOSCOPE TECHNOLOGIES, LLC · 2020 · $779,869

## Abstract

Geographic atrophies (GA) in dry-age related macular degeneration (AMD) is characterized by degeneration of
photoreceptors, and is the leading cause of new vision loss in ~15 million persons. There is neither a cure that
can stop the degeneration nor a therapy to restore vision loss. We have developed ambient-light activatable
multi-characteristic opsin (MCO-II) to allow stimulation of retinal ganglion cells (RGCs) for vision rehabilitation.
However, clinical translation of such gene therapy to patients with GA will require targeted delivery of opsin-
encoding genes into the atrophic regions without perturbing remaining functional retina. Therefore, we have
developed a near-infrared laser based efficient method for in-vivo targeted gene delivery into retina. In this
Nano-enhanced Optical Delivery (NOD) method, we utilize surface plasmon resonance based field
enhancement by functionalized gold nanorods (fGNRs) to transiently perforate cell membrane to deliver the
molecules. In the Phase I, we demonstrated targeted in-vivo optical delivery of MCO-II to degenerated retina in
mice using NOD at multiple wavelengths. Further, we made comparative study of continuous wave (cw) and
nanosecond pulsed laser based NOD of MCO-II plasmids and determined optimized laser parameters for
efficient transfection of retina. No detectable ocular damage was observed due to NOD. Further, the
immunostaining of retina after in-vivo NOD of MCO-II plasmids showed no noticeable cell death.
Electrophysiology studies demonstrate that MCO-II sensitized cells are activatable by light, allowing visually
evoked cortical activities. The overall goal of this Phase-II proposal is to develop the combination NOD product
for photosensitizing RGCs in the degenerated retina in a safe manner and stimulating photosensitized RGCs
by ambient light for vision rehabilitation. Towards this goal we have following aims: (1) Quantify long-term
stability and safety of NOD in mice model lacking photoreceptors; (2) Evaluate functioning of targeted retinal
regions after re-photosensitization of RGCs using NOD assisted MCO-II delivery in mice and rat models; and
(3) GLP study of toxicity, biodistribution and efficacy of NOD-delivered MCO-II plasmids in non-human
primates (NHPs). This collaborative proposal brings together complementary expertise in optical delivery,
optogenetics, ophthalmology, instrument, molecular biology, nanomaterials, retina biology and function,
neuroscience/behavior, electrophysiology, biostatistics, and toxicology to address the challenge in retinal
degeneration. The safety/efficacy study in NHPs will be performed at CRO facility. Upon completion of the
Phase II we envision to advance: (i) NOD product development for clinical studies, (ii) IND application to FDA,
and (iii) partnering with venture capital and Pharma company for commercialization. Success of this proposal
will lead to a new clinical approach for treating patients with GA by conventional intravitreal injection of f...

## Key facts

- **NIH application ID:** 10011324
- **Project number:** 1R44EY031642-01
- **Recipient organization:** NANOSCOPE TECHNOLOGIES, LLC
- **Principal Investigator:** Samarendra Kumar Mohanty
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $779,869
- **Award type:** 1
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011324

## Citation

> US National Institutes of Health, RePORTER application 10011324, Targeted Nano-enhanced Optical Delivery of opsin for dry-AMD therapy (1R44EY031642-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10011324. Licensed CC0.

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