mRNA Ocular Delivery via Nanoparticle Barriers

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Solution Overview

Problem

Current therapies for ocular diseases face challenges due to the unique anatomy and physiology of the eye, which pose barriers to effective drug delivery, including static and dynamic barriers that hinder the distribution of therapeutic agents.

Innovation Solution

The use of messenger RNA (mRNA) therapy for delivering therapeutic proteins directly to the eye through various administration routes, such as intravitreal, intracameral, subconjunctival, subtenon, retrobulbar, topical, and posterior juxtascleral administration, utilizing lipid or polymer-based nanoparticles to ensure effective protein expression and activity within the eye.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional drug delivery methods are used for ocular diseases, then the treatment approach is simple and direct, but the static and dynamic barriers of the eye (anatomy and physiology) prevent effective drug distribution and protein expression

Engineering Contradiction:
Improveeffective drug deliveryVSAvoiddelivery system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Lipid or polymer-based nanoparticles are used as intermediary carriers to deliver mRNA across the eye's static and dynamic barriers. These nanoparticles protect the mRNA from degradation, facilitate cellular uptake, and enable effective protein expression in ocular tissues despite the challenging anatomical and physiological barriers.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the physical and chemical parameters of the therapeutic agent by using mRNA encapsulated in nanoparticles instead of conventional proteins or small molecules. This parameter change enables the therapeutic to overcome barriers that would otherwise prevent effective delivery and sustained expression in the eye.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If mRNA therapy is used to achieve robust protein expression in the eye, then effective treatment of ocular diseases is achieved, but the complexity of delivery through static and dynamic barriers increases

Engineering Contradiction:
Improveprotein expression levelVSAvoidmRNA delivery system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

Nanoparticles serve as mediators that protect mRNA from enzymatic degradation in the ocular environment and facilitate its delivery to target cells. This intermediary approach enables robust protein expression while managing the complexity of delivering fragile mRNA molecules through the eye's barriers.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The lipid or polymer-based nanoparticle shells provide a flexible protective structure that encapsulates the mRNA, allowing it to navigate through the eye's static and dynamic barriers while maintaining structural integrity and enabling sustained protein expression.

Inventive Principle:
Principle #30Flexible shells and thin films

3Adaptability or versatility

If multiple administration routes (intravitreal, intracameral, subconjunctival, etc.) are utilized for mRNA delivery, then effective treatment coverage is improved, but the complexity of administration procedures increases

Engineering Contradiction:
Improveadministration route flexibilityVSAvoidadministration procedure simplicity
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The nanoparticle-mRNA formulation is designed with universal applicability across multiple administration routes (intravitreal, intracameral, subconjunctival, subtenon, retrobulbar, topical, and posterior juxtascleral). This multi-functional design allows the same therapeutic composition to be effectively delivered through different routes depending on the specific ocular condition and clinical requirements.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentUS20220354968A1mRNA therapy for the treatment of ocular diseases
Publication Date: 2022.11.10 TRANSLATE BIO INC
  • US20220354968A1 patent drawing
  • US20220354968A1 patent drawing
  • US20220354968A1 patent drawing

AI summary

The present invention provides, among other things, a method of ocular delivery of messenger RNA (mRNA), comprising administering into an eye of a subject in need of delivery a composition comprising an mRNA encoding a protein, such that the administration of the composition results in expression of the protein encoded by the mRNA in the eye.