Biodegradable Polymeric Nanoparticles for Suprachoroidal Gene Delivery
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Solution Overview
Problem
Current ocular gene transfer methods using viral vectors for delivering therapeutic agents to the eye face challenges such as immune responses, limited cargo capacity, and invasive procedures, while nonviral gene transfer with biodegradable particles has lower transfection efficiency and is less effective compared to viral vectors.
Innovation Solution
Administering a composition comprising nanoparticles or microparticles, specifically poly(beta-amino ester) (PBAE) or PEG-PBAE polymers, to the suprachoroidal space to facilitate targeted and sustained delivery of therapeutic agents, including genes and proteins, to treat various eye diseases, allowing for repeated injections and larger gene replacement capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If viral vectors are used for ocular gene transfer, then transfection efficiency and sustained expression are improved, but immune response and limited cargo capacity worsen
Solution Approach 1:
The patent uses biodegradable polymeric nanoparticles instead of viral vectors. These synthetic particles are designed to be transient and biodegradable, avoiding the persistent immune responses associated with viral vectors while maintaining sufficient transfection efficiency for therapeutic purposes.
Solution Approach 2:
The patent employs composite polymeric nanoparticles that combine multiple functional components within a single particle system. This allows integration of transfection capability, cargo protection, and controlled release properties without requiring viral envelope proteins that trigger immune responses.
2Duration of action of moving object
If viral vectors are used for ocular gene transfer, then long-term expression is improved, but repeated administration worsens due to immune response
Solution Approach 1:
The biodegradable polymeric nanoparticles are designed to degrade after delivering their cargo, allowing the system to be safely re-administered multiple times without accumulating immune responses. Each particle completes its function and degrades, resetting the system for future treatments.
Solution Approach 2:
The patent modifies the physical and chemical parameters of the delivery system by using biodegradable polymers with controlled degradation rates. This allows tuning of the expression duration to match therapeutic needs while maintaining compatibility with repeated administrations.
3Object-generated harmful factors
If nonviral gene transfer with biodegradable particles is used, then immune response is reduced, but transfection efficiency worsens
Solution Approach 1:
The patent designs composite polymeric nanoparticles that integrate multiple functions: the polymeric structure provides biodegradability and low immunogenicity, while embedded cationic components enable efficient DNA/RNA complexation and cellular transfection. This composite approach overcomes the traditional efficiency limitation of nonviral systems.
Solution Approach 2:
The patent optimizes parameters such as particle size, surface charge, and polymer composition to enhance transfection efficiency. By adjusting these parameters, the system achieves viral-level efficiency without the immunogenicity of viral vectors.
4Quantity of substance
If nonviral gene transfer is used, then cargo capacity is improved, but transfection efficiency worsens
Solution Approach 1:
The patent modifies the polymeric structure and physical parameters of the nanoparticles to accommodate large cargo molecules such as full-length retinal genes. The polymer composition and particle architecture are optimized to protect and efficiently deliver these large cargo payloads while maintaining transfection efficiency.
Data Source
AI summary
The presently disclosed subject matter provides compositions and methods for administering a nanoparticle or microparticle and a therapeutic agent to the suprachoroidal space in the eye.