This technology employs an engineered self-delivering siRNA to selectively reduce USP10 protein levels in tissues, thereby promoting regenerative healing and suppressing pathological scarring. Preclinical studies in the eye demonstrate a favorable safety profile and robust efficacy, supporting the potential of this approach for treating fibrotic disease across multiple organ systems.
Background: Regenerative healing, particularly in ocular tissues such as the transparent cornea, is a critical area of biomedical research due to the eye’s limited capacity for self-repair and the high risk of vision loss following injury or surgery. Scarring and fibrosis in the cornea can result in permanent visual impairment or blindness, making effective wound healing without scarring a major unmet medical need. Current clinical approaches to treat corneal scarring are limited, with corneal transplantation being the only definitive solution for severe cases. Additionally, in glaucoma surgeries like trabeculectomy, excessive scarring of the surgical site often leads to surgical failure and poor patient outcomes. The need for therapies that can promote regenerative healing while minimizing fibrosis is therefore urgent, not only for ocular health but also for broader applications in tissue repair and organ fibrosis. Existing methods to prevent or treat scarring in the eye, such as the use of antiproliferative agents like mitomycin C, are associated with significant drawbacks, including toxicity, risk of infection, and non-specific inhibition of cell proliferation that can impair normal healing. These treatments do not specifically target the molecular drivers of fibrosis and often result in incomplete or unsatisfactory outcomes. Furthermore, the lack of targeted, non-toxic therapies means that patients frequently require repeated interventions or long-term use of adjunctive medications such as steroids and antibiotics, which carry their own risks and side effects. The limitations of current approaches highlight the need for more precise, effective, and safer therapies that can modulate specific molecular pathways involved in scarring and promote tissue regeneration.
Technology Overview: This technology comprises a self-delivering small interfering RNA (siRNA) therapeutic designed to selectively suppress ubiquitin-specific peptidase 10 (USP10), thereby shifting wound repair toward regenerative healing and away from fibrosis, with particular relevance to corneal and other ocular tissues. The siRNA duplex is chemically modified for enhanced stability, specificity, and delivery efficiency. The technology has demonstrated potent knockdown of USP10 in cell-based assays, significant acceleration of wound closure, and reduction of fibrosis markers in animal models, as well as enhanced epithelial regeneration in ex vivo human corneas. Safety studies in mice, rabbits, and mini-pigs confirmed the absence of toxicity or adverse ocular effects, supporting its suitability for clinical applications. What differentiates this solution is its combination of a novel therapeutic target (USP10) with a highly optimized, self-delivering siRNA platform that achieves effective gene silencing at lower doses and with minimal dosing frequency. Unlike traditional anti-scarring treatments, which often rely on cytotoxic agents like mitomycin C and carry significant side effects, this approach directly modulates the molecular pathways involved in fibrosis and healing, promoting nerve growth, enabling regenerative repair without the risk of immune or vascular complications. The extensive chemical modifications confer nuclease resistance and improved pharmacokinetics, allowing for topical or parenteral administration without the need for complex delivery vehicles. The platform’s efficacy across multiple preclinical models, broad applicability to various fibrotic conditions, and favorable safety profile position it as a transformative advance in regenerative medicine, potentially reducing the need for invasive procedures like corneal transplantation and offering a new paradigm for treating scarring and fibrosis in both ocular and non-ocular tissues.
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Advantages: • Promotes regenerative healing and significantly reduces scarring, especially in corneal tissues • Self-delivery siRNA technology enables effective USP10 knockdown at low doses without immune or vascular reactions • Demonstrated safety and non-toxicity in preclinical animal models with no adverse effects on corneal morphology or function • Long-lasting efficacy with effects sustained for at least six weeks post-treatment • Potential to improve outcomes in ocular surgeries by preventing fibrosis and scarring that lead to vision loss • Versatile delivery options including topical, pulmonary, and parenteral administration with targeted delivery capabilities • Broad therapeutic applications beyond ocular healing, including treatment of fibrosis in skin and internal organs • Reduces need for adjunctive antibiotic or steroid treatments due to its targeted and effective mechanism
Applications: • Corneal wound healing therapy • Anti-scarring treatment post-eye surgery • Topical therapy for ocular fibrosis • Dermal wound regenerative healing • Fibrosis treatment in internal organs
Intellectual Property Summary: Patent application PCT/US2025/018729 filed on 3/6/2025
Stage of Development: TRL5 Supported by data appropriate to its current TRL stage, including compelling efficacy in several preclinical models, broad fibrotic disease applicability, and a strong safety profile, the platform stands poised to drive a major advance in regenerative medicine, offering a less invasive alternative to procedures such as corneal transplantation and a novel pathway for treating fibrosis across tissue types.
Licensing Status: This technology is available for licensing.