Platform Delivery Technology for Nucleic Acid Therapeutics to Promote Wound Healing

PROJECT SUMMARY RNA interference RNAi a process in which small interfering siRNA molecules inhibit gene expression is of broad therapeutic potential in the treatment of a variety of diseases but is presently hampered by delivery challenges including susceptibility of siRNA degradation rapid clearance and cell impermeability Local delivery circumvents some of these challenges but siRNA must still be protected from degradation and effectively enter target cells within the tissue of interest Thus there remains a significant unmet need for platform delivery technologies capable of controlled and effective in vivo delivery of siRNA LayerBio proposes to develop new delivery approach for siRNA therapeutics based on its proprietary LayerForm technology LayerForm is a coating process based on a layer by layer LbL nanofabrication technique that stably incorporates nucleic acid therapeutics from water into a thin polymer coating atop a surface The polymer coating is engineered to erode at physiologically relevant time scales delivering siRNA or other drugs to target tissue LayerForm offers the following benefits i precise control of siRNA dosing and release ii effective transfection of nucleic acids iii fully biocompatible materials iv modular platform capable of delivery of a variety of nucleic acids and v facile processing The use of siRNA based strategies in regenerative medicine and tissue engineering is a promising application of RNA interference where effective therapeutics to promote wound healing would offer a significant health benefit Typical wounds would require local delivery of siRNA where the LayerForm delivery technology is well suited LayerBio has developed siRNA incorporated LbL coatings atop wound dressings to accelerate the healing of chronic wounds An siRNA oligonucleotide has been selected for modulation of key targets that coordinate a cascade of events that occur during normal wound healing but are impaired in chronic wounds During in vivo feasibility studies LayerForm siRNA LbL coated dressings demonstrated accelerated wound healing in diabetic mice This Phase project will further advance its LayerBioandapos s technology platform toward clinical translation by demonstrating feasibility for process scale up Further current siRNA LbL formulations are fabricated atop non degradable nylon mesh that must be removed from the wounds LayerBio will fabricate siRNA LbL films atop suitable bioresorbable dressing materials capable of being absorbed into the wound These advancements will be validated in an in vivo study for efficacy in a diabetic mouse model of wound healing Results of this Phase effort will form the basis for Phase optimization process scale up and toxicology testing Success in this project will also motivate the expansion of LayerBioandapos s technology platform for delivery of other nucleic acid therapeutics and other disease indications PROJECT NARRATIVE Nucleic acid based therapies have broad therapeutic potential in treating a variety of diseases that are particularly hard to address with existing drugs however development of such therapies is stalled by the lack of suitable methods for delivery of such therapeutics to diseased tissue This application seeks to develop new drug delivery technology for nucleic acid therapeutics that will improve their stability and ability to reliably reach target tissue The utility of this drug delivery technology will be demonstrated by generating novel wound dressings that release nucleic acid therapeutics to promote rapid closure and healing of wounds A product that successfully promotes healing could provide a significant health benefit where healing is impaired and could substantially reduce the burden of healthcare costs