2022 Photonics West, “Ultrafast Laser Based Transient Perforation of Cellular Membranes for in Vivo Neuromodulation” by Samarendra Mohanty, PhD
Neuronal dysfunction due to lack of functional copy of specific genes leads to several neurological disorders, and gene replacement or editing based therapies require efficient gene delivery. Further, activation of specific cells by optical, ultrasound and other methods requires insertion of gene-encoding actuators into cells. I will present use of near-infrared ultrafast laser microirradiation platform for efficient and spatially-targeted delivery of different therapeutic genes to neuronal tissue. Specifically, I will describe use of this platform for delivery of gene encoding for neuroprotective and anti-angiogenic PEDF molecule to retina that exhibited protection from different insults. Ultrafast laser based delivery of ambient-light activatable multi-characteristic opsin (MCO) to retinal cells led to functional improvement, measured by electrophysiology. Besides, targeted delivery, the ultrafast laser based non-viral gene delivery could circumvent the payload limitation of AAV-based delivery, and large genes such as ABCA4 (mutation of which leads to photoreceptor dysfunction) could be delivered to retina. In-vivo neuromodulation by ultrafast laser based perforation of cell membrane opens up new possibilities such as redosing in subjects requiring gene transfer without causing inflammatory or immune response.
2022 SPIE BIOS, “Multi-Characteristic Opsin Restores Vision In Stargardt Mice Model.” Sanghoon Kim, PhD
Stargardt Disease is an inherited macular degeneration caused by mutation of genes, primarily ABCA4 in the photoreceptor cells leading to their dysfunction and degeneration in the macula. Here, we report results of ambient-light vision restoration in Stargardt mice (Abca4tm1Ght/J) upon intravitreal delivery of AAV-carried MCO (vMCO) as evaluated by electrophysiology, Optical Coherence Tomography (OCT) and visually guided behavior. Further, safety of MCO-enabled vision restoration therapy was evaluated by measurement of Intraocular Pressure, OCT and Immunohistochemistry. The vMCO based ambient light activatable optogenetic therapy has potential to be a disease-agnostic therapy to address the unmet need of inherited retinal degenerative diseases.
2022 SPIE BIOS, “Spatially Targeted Non-Viral Optical Delivery of Opsin-Encoding Genes Into Primate Retina.” Sanghoon Kim, PhD
Degeneration of photoreceptors, retinal cells including retinal pigment epithelium, and retinal ganglion cells characterizes visual disorders involving retinal dysfunction. The efficient and targeted gene delivery into retinal cells is critical for treatment of a variety of visual disorders. Here, we report use of an OCT guided, spatially targeted, near-infrared laser microirradiation platform to successfully deliver genes encoding ambient-light activatable multi-characteristic opsin (MCO) to retinal cells in non-human primates. The efficacy of gene delivery was evaluated by fundus imaging of the reporter (mCherry) fluorescence, and immunohistochemistry. Functional improvement was measured by red-ERG which was attributed to MCO’s broadband activation spectrum.
2021 ARVO, “OCT Guided Micro-Focal ERG.” Michael Carlson, BSE and Nanoscope Associates
2021 ARVO, “Applying Stem Cell Theranostic Platforms For Retinal Regenerative Therapies”. Valeria Canto-Soler PhD, University of Colorado and Nanoscope Associates. This presentation highlights recent advances in non-invasive in vivo functional monitoring of stem cell-derived 3D retinal tissues. Here is a link to Dr. Canto-Soler’s Video:
2021 SPIE, “Retinal Dystrophy Model Using Laser Microirradiation“, Michael Carlson, BS and Nanoscope Associates
2021 ARVO, “OCT Guided Microirradiation“, Sanghoon Kim, PhD and Nanoscope Associates
2021 ARVO, “Optical Coherence Tomography Guided Laser Gene Delivery In Degenerated Retina”, Biraj Mahato, PhD and Nanoscope Associates
2020 Brain Initiative, “Laser Gene Delivery” Sanghoon Kim, PhD and Nanoscope Associates
2019 ARVO, “Multifractal Functional OCT”, Subrata Batabyal, PhD and Nanoscope Associates