Intraocular Gene Therapy Delivery via Electric-Current Vector Mobility

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Solution Overview

Problem

Current methods for delivering gene therapy vectors to the eye, such as subretinal injection and intravitreal injection, face challenges in achieving efficient and widespread transduction of retinal cells, particularly due to tissue barriers and the risk of injury.

Innovation Solution

The use of intravitreal injection combined with the application of an electric current, known as electric-current vector mobility (ECVM), to enhance the delivery and transduction efficiency of adeno-associated viral (AAV) vectors in the retina.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If subretinal injection is used to deliver AAV vectors, then transduction efficiency of RPE and photoreceptors is improved, but risk of injury and infection increases

Engineering Contradiction:

Improvetransduction efficiencyVSAvoidrisk of injury

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses the vitreous humor as an intermediary medium to deliver AAV vectors to the retina. Instead of directly injecting into the subretinal space, vectors are injected into the vitreous cavity where they can diffuse and be transported to target cells, reducing mechanical injury risk while maintaining transduction efficiency through the intermediary vitreous pathway

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical direct injection method (subretinal) with a diffusion-based delivery system (intravitreal). By substituting the mechanical penetration approach with a diffusion and transport mechanism through the vitreous humor, the method reduces tissue disruption and injury risk while achieving vector delivery to retinal cells

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Object-affected harmful factors

If intravitreal injection is used to deliver AAV vectors, then risk of injury is reduced, but transduction efficiency of outer retina cells deteriorates

Engineering Contradiction:

Improverisk of injuryVSAvoidtransduction efficiency

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent employs periodic or extended duration low-level electric current application following intravitreal injection. This periodic electrical stimulation enhances vector transport over time, allowing sustained improvement in transduction efficiency of outer retina cells without requiring high-intensity single-pulse stimulation that would cause injury

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The patent changes the physical parameters of vector delivery by applying electric current to alter the mobility and transport characteristics of AAV vectors in the vitreous humor. By modifying the electrical parameters (current intensity, duration, frequency), the method enhances vector migration to outer retina cells while maintaining the safety advantages of intravitreal injection

Inventive Principle:

Principle #35Parameter changes

3Reliability

If surgical ILM peeling is performed to enhance vector transduction, then transduction efficiency is improved, but device complexity and invasiveness increase

Engineering Contradiction:

Improvetransduction efficiencyVSAvoidsurgical complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent enables the vector delivery system to overcome the ILM barrier through self-powered electrophoretic transport. The AAV vectors themselves are transported across the ILM by applying low-level electric current, eliminating the need for surgical peeling procedures. The system serves itself by using electrical energy to drive vector migration through tissue barriers that would otherwise require mechanical removal

Inventive Principle:

Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

ECVM significantly improves the transduction efficiency of AAV vectors in the retina, achieving results comparable to or better than subretinal injection while minimizing the risk of injury and infection.

Implementation Method 1

Methodology Applied

Scientific EffectElectrophoresis: Electrophoresis

Data Source

PatentEP3823567B1Intraocular injection of gene therapy expression vectors

Publication Date: 2025.06.18 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

Figure 1A~1B
Figure 1C~2A
Figure 2B~2D

AI summary

Methods of administering a gene therapy construct to the eye including injection of the construct into the eye and application of an electric current to enhance penetration of or cellular expression of molecules in ocular tissues. These methods provide effective technique for the intraocular delivery of gene therapy vectors, especially AAV vectors, and nanoparticles.