Engineered sensor actuator modulator as aqueous humor outflow actuator for gene therapy of primary open-angle glaucoma.

Glaucoma, a blinding eye disease with optic neuropathy, is usually associated with elevated intraocular pressure (IOP). The currently available pharmacological and surgical treatments for glaucoma have significant limitations and side effects, which include systemic reactions to medications, patient non-compliance, eye infections, surgical device failure, and damage to the eye. Here, we present Sensor-Actuator-Modulator (SAM), an engineered double mutant version of the bacterial stretch-activated mechanosensitive channel of large conductance (MscL) that directly senses tension in the membrane lipid bilayer of cells and in response, transiently opens its large nonspecific pore to release cytoplasmic fluid.

Shaping the future US bioeconomy through safety, security, sustainability, and social responsibility.

Biomanufacturing practitioners and researchers describe the norms that should govern the growing, global field, to include safety, security, sustainability, and social responsibility. These '4S Principles' should be broadly adopted so that the future of the field may provide the greatest benefits to society.

Biodistribution of adeno-associated virus type 2 carrying multi-characteristic opsin in dogs following intravitreal injection.

Gene therapy of retinal diseases using recombinant adeno-associated virus (rAAV) vector-based delivery has shown clinical success, and clinical trials based on rAAV-based optogenetic therapies are currently in progress. Recently, we have developed multi-characteristic opsin (MCO), which has been shown to effectively re-photosensitize photoreceptor-degenerated retina in mice leading to vision restoration at ambient light environment. Here, we report the biodistribution of the rAAV2 carried MCO (vMCO-I) in live samples and post-mortem organs following intraocular delivery in wild-type dogs.

Near-Infrared Laser-Based Spatially Targeted Nano-enhanced Optical Delivery of Therapeutic Genes to Degenerated Retina.

Non-viral delivery of therapeutic genes into targeted areas of retina is essential for re-functionalizing the retinal circuitry. While a focused ultrafast laser beam has been recently used for intra-ocular delivery of molecules, it poses the significant technical challenge of overcoming aberrations of the eye and maintaining a tightly focused spot on the retinal cell membrane. Furthermore, to minimize collateral damage and increase the throughput of gene delivery, we introduced a weakly focused near-infrared (NIR) continuous wave (CW) or pulsed laser beam on to the cells wherein the intensity is locally enhanced by gold nanorods bound to the cell membranes to permit gene insertion.