Ultrafast Laser Based Transient Perforation of Cellular Membranes for in Vivo Neuromodulation

Presented by Samarendra Mohanty, PhD at Photonics West 2022

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.