Inner Ear Gene Delivery via Cerebrospinal Fluid

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Solution Overview

Problem

Current therapies for hearing loss, including hearing aids and cochlear implants, are insufficient in restoring full auditory function, and gene therapy beyond the post-natal stage has proven unsuccessful and invasive.

Innovation Solution

A polynucleotide comprising a regulatory sequence identical to a promoter or enhancer sequence of specific genes, operably linked to a transgene, delivered via a nucleic acid vector, such as an adeno-associated virus, to the inner ear through the cerebrospinal fluid route.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If gene therapy is administered through intracochlear or intravestibular injections, then hearing can be restored in post-natal models of genetic deafness, but the procedure is invasive and can cause damage to inner ear structures

Engineering Contradiction:

Improvehearing restorationVSAvoiddamage to inner ear structures

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses the cerebrospinal fluid (CSF) as an intermediary medium to deliver the AAV vector containing the therapeutic transgene to the inner ear. Instead of directly injecting into the cochlea or vestibule, the composition is administered into the CSF space, which then transports the therapeutic agent to the inner ear tissues, thereby avoiding direct invasive contact with delicate inner ear structures while still achieving effective gene delivery and hearing restoration

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If gene therapy is administered beyond the post-natal stage, then therapeutic intervention is possible for older subjects, but the procedure has proven unsuccessful with invasive methods

Engineering Contradiction:

Improvetherapeutic windowVSAvoidtherapy success rate

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent changes the delivery parameter from direct intracochlear/intravestibular injection to cerebrospinal fluid administration. This parameter change enables successful gene therapy delivery in adult subjects beyond the post-natal stage, where previous invasive methods had failed. The CSF route provides a non-invasive pathway that overcomes the limitations of age-related barriers to gene delivery

Inventive Principle:

Principle #35Parameter changes

3Reliability

If hearing aids or cochlear implants are used, then auditory function can be improved, but full auditory capacities cannot be restored

Engineering Contradiction:

Improveauditory function improvementVSAvoidfull auditory capacity restoration

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the mechanical systems of hearing aids and cochlear implants with a biological gene therapy approach. Instead of using external devices to amplify or electrically stimulate hearing, the invention delivers a therapeutic transgene that corrects the underlying genetic defect, enabling the inner ear structures to function naturally and restore full auditory capacities

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20250073354A1Compositions and methods for delivery of agents to inner ear

Publication Date: 2025.03.06 UNIVERSITY OF ROCHESTER

AI summary

This disclosure relates compositions and methods to delivery of various agents to the inner ear of a subject.