I-Corps: Anti-Fibrotic Self-Delivering siRNA Therapeutics

Suny, Upstate Medical University, Syracuse NY

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project is the development of a potential therapeutic treatment that promotes healing with significantly decreased scarring. Fibrosis and scarring are the accumulation of excess extracellular matrix components, which is a pathological component of a wide spectrum of clinical indications including scleroderma and fibrosis of the heart, lung, liver, cornea, and skin. Approximately one-third of all fatalities are associated with fibrotic outcomes, which represents a significant problem and market opportunity. The initial focus of the proposed technology is corneal and dermal scarring. Cornea and skin have a similar treatment modality by administration of a topical solution. Cornea and skin may serve as model tissues for studying the pathobiology of fibrosis in all tissues, and may lead to expansion into other indications with fibrotic underpinnings such as pulmonary fibrosis, non-Alcoholic Steatohepatitis (NASH), cardiovascular disease, and neurodegenerative diseases. This I-Corps project is based on the development of a self-delivery siRNA therapeutic treatment to prevent scarring and fibrosis. A genetic target has been identified that slows pathology and supports regenerative healing of wounded cornea and skin, two model tissues of fibrosis. Data show target knockdown in corneal and skin wounding models promotes regenerative healing, a type of wound healing with limited to no scarring. The current standard of care, topical administration of steroids to wounds (cornea and skin), yields unpredictable, mixed results, that vary widely between increased rates of healing, no effect, or decreased healing rates. The proposed technology uses topical administration of a siRNA that effectively penetrates cells and functions as both an anti-inflammatory and anti-scarring agent for topical wounds. The proposed therapeutic is optimized to penetrate tissues and is designed to be efficacious for 2-3 months with a single dose, which may revolutionize subretinal scarring and systemic fibrotic diseases. In addition, in vivo results in small and large animal models demonstrate efficacy and also present favorable safety profiles with no evidence of cellular/tissue toxicity, which may lead to a treatment for scarring and fibrosis. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.