Optical coherence tomography guided targeted non-viral optical delivery of opsin-encoding genes into the retina
- 1Nanoscope Technologies LLC.
- 2Nanoscope Therapeutics, Inc.
Abstract
Introduction: Retinal degenerative diseases cause progressive photoreceptor loss while leaving populations of inner retinal neurons available for optogenetic intervention. However, efficient and spatially controlled non‐viral gene delivery to these surviving cells remains challenging. We evaluated optical coherence tomography (OCT)‐guided nano-enhanced optical delivery (NOD) for targeted delivery of the multi-characteristic opsin MCO‐020 to the degenerative retina.
Methods: NOD uses plasmonic gold nanorods (GNRs) and a 980‐nm near‐infrared laser to transiently permeabilize cell membranes and facilitate localized plasmid delivery. Delivery parameters were initially optimized in HEK293 cells. In vivo efficacy and safety were subsequently evaluated in rd1 mice following intravitreal administration of MCO-020 plasmid and GNRs followed by OCT‐guided laser delivery. Transgene expression, retinal structure, retinal and cortical electrophysiological responses, intraocular pressure, retinal‐cell viability, and biodistribution were evaluated.
Results: In vitro studies demonstrated laser‐dependent and spatially restricted MCO‐020 expression without detectable cytotoxicity within the tested operating range. In vivo , OCT‐guided NOD produced MCO‐020 expression in inner retinal cells within targeted retinal regions without detectable changes in retinal structure or thickness. MCO‐020‐treated mice demonstrated increased light‐evoked retinal and visually evoked cortical responses compared with untreated controls, with responses and transgene expression remaining detectable through the 52‐week observation period. Retinal‐cell viability, intraocular pressure, and complementary electrophysiological safety assessments showed no detectable treatment-associated adverse effects. Biodistribution analysis showed only low levels of vector DNA in evaluated non‐target tissues.
Discussion: These findings demonstrate that OCT‐guided NOD can provide spatially targeted, non‐viral delivery of an opsin‐encoding plasmid to the degenerative retina while preserving retinal structure and supporting sustained functional engagement of the visual pathway. The approach may provide a platform for localized delivery of therapeutic genes to retinal regions affected by degeneration.
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BibTeX
@article{kim2026optical,
title = {{Optical coherence tomography guided targeted non-viral optical delivery of opsin-encoding genes into the retina}},
author = {Sanghoon Kim and Michael Carlson and Subrata Batabyal and Adnan Dibas and Samarendra Mohanty},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1831339},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1831339/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Optical coherence tomography guided targeted non-viral optical delivery of opsin-encoding genes into the retina
AU - Sanghoon Kim
AU - Michael Carlson
AU - Subrata Batabyal
AU - Adnan Dibas
AU - Samarendra Mohanty
PY - 2026
DA - 2026/10/19
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1831339
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1831339/full
AB - Introduction: Retinal degenerative diseases cause progressive photoreceptor loss while leaving populations of inner retinal neurons available for optogenetic intervention. However, efficient and spatially controlled non‐viral gene delivery to these surviving cells remains challenging. We evaluated optical coherence tomography (OCT)‐guided nano-enhanced optical delivery (NOD) for targeted delivery of the multi-characteristic opsin MCO‐020 to the degenerative retina. Methods: NOD uses plasmonic gold nanorods (GNRs) and a 980‐nm near‐infrared laser to transiently permeabilize cell membranes and facilitate localized plasmid delivery. Delivery parameters were initially optimized in HEK293 cells. In vivo efficacy and safety were subsequently evaluated in rd1 mice following intravitreal administration of MCO-020 plasmid and GNRs followed by OCT‐guided laser delivery. Transgene expression, retinal structure, retinal and cortical electrophysiological responses, intraocular pressure, retinal‐cell viability, and biodistribution were evaluated. Results: In vitro studies demonstrated laser‐dependent and spatially restricted MCO‐020 expression without detectable cytotoxicity within the tested operating range. In vivo , OCT‐guided NOD produced MCO‐020 expression in inner retinal cells within targeted retinal regions without detectable changes in retinal structure or thickness. MCO‐020‐treated mice demonstrated increased light‐evoked retinal and visually evoked cortical responses compared with untreated controls, with responses and transgene expression remaining detectable through the 52‐week observation period. Retinal‐cell viability, intraocular pressure, and complementary electrophysiological safety assessments showed no detectable treatment-associated adverse effects. Biodistribution analysis showed only low levels of vector DNA in evaluated non‐target tissues. Discussion: These findings demonstrate that OCT‐guided NOD can provide spatially targeted, non‐viral delivery of an opsin‐encoding plasmid to the degenerative retina while preserving retinal structure and supporting sustained functional engagement of the visual pathway. The approach may provide a platform for localized delivery of therapeutic genes to retinal regions affected by degeneration.
SN - 1663-9812
ER -