Controlled-Release Polymer Gel for Safe and Targeted Retinal Gene Therapy
This invention is a novel polymer-based gel implant, which comprises a therapeutic agent suspended within a water-absorbing polymer component that remains in a gel phase at ambient temperature. Its most significant advantage is providing a means for safe, controlled, and targeted delivery of treatments, including gene therapy vectors, to the retina while avoiding undesirable diffusion or the high immunogenicity associated with current injection methods.
Description
The core technology is a polymer-based gel implant designed for targeted delivery of therapeutic agents, such as gene therapy vectors, to the ocular region. The material is composed of a polymer component and a therapeutic agent suspended in water. The innovation lies in the polymer's phase transition property: the material is a hydrated gel at ambient temperature, which allows for safe, precise, and non-diffusive implantation. Once implanted at body temperature, the polymer component is capable of absorbing water and transitions from a gel to a liquid phase as its concentration decreases. This natural dissolution provides for the controlled and timely release of the therapeutic agent over a specific period, completing its transition to a liquid phase within 24 hours. For enhanced targeting, the gel implant can be optionally modified with a backing layer to promote unidirectional delivery of the agent directly to the retina, preventing undesirable diffusion to other parts of the eye.Applications
- Delivery system for retinal gene therapy treatments (e.g., using AAV vectors).- Therapies for Age-related Macular Degeneration (AMD), addressing both the wet and currently untreatable dry forms.
- Treatments for Diabetic Retinopathy and other vascular retinopathies.
- Treatment of inherited retinal degenerations, such as Leber Congenital Amaurosis (LCA).
- Delivery vehicle for advanced therapeutics like CRISPR/Cas9 components to target cells in the retina.
Advantages
- Enables safe and controlled delivery of therapeutic agents, including gene therapy vectors, to the desired ocular region.- Eliminates a permanent foreign body with an engineered phase transition that allows the gel to dissolve into a liquid over a predictable time at body temperature.
- Reduces off-target delivery and minimizes systemic immune response by safely localizing the treatment without undesired diffusion.
- Increases therapeutic efficacy by successfully retaining the activity of the released vector, as demonstrated in in vitro testing with adeno-associated virus (AAV) vectors.
- Provides a less-invasive alternative to current high-dose intravitreal injections and highly invasive subretinal injections for retinal therapy.
Invention Readiness
The invention is at an advanced preclinical stage, having successfully demonstrated key functional principles and safety in relevant biological environments. Generated data includes in vitro evidence that the therapeutic agent, such as an AAV vector, retains its activity after release. Crucially, in vivo studies in a primate model confirmed the intended mechanism: the implant fully transitions to a liquid phase and is released without causing toxicity or adverse immune response, successfully delivering a gene to the target retinal cells and resulting in expression in the fovea after two months. Further studies will focus on final optimization and scale-up toward full-scale system demonstration and Investigational New Drug (IND)-enabling regulatory work.IP Status
https://patents.google.com/patent/WO2023091412A1Related Publication(s)
Ziaei, P., Resnick, J. L., Stella, N., & DiLeo, M. V. (2022). Novel Combined Lidocaine/Povidone Iodine Delivery System for Preintravitreal Injection. Journal of Ocular Pharmacology and Therapeutics, 38(4), 319–325. https://doi.org/10.1089/jop.2021.0095