DFNB59 AAV Gene Delivery for Restoring Auditory Nerve Signaling

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Solution Overview

Problem

Current treatments for auditory neuropathy spectrum disorder (ANSD) are inadequate, as they do not effectively address the impaired auditory signal transmission to the brainstem, leading to poor speech perception and hearing loss out of proportion to hearing levels, and are hindered by inefficient gene delivery methods to inner ear cells.

Innovation Solution

A gene therapy using an adeno-associated virus (AAV) vector, specifically the Anc80 capsid, delivers the DFNB59 gene with the G292R mutation, guided by promoters like Espin, PCDH15, or PTPRQ, to restore auditory nerve signaling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If conventional gene delivery methods are used to treat ANSD, then the treatment approach is simple, but the gene delivery efficiency to inner ear cells is low

Engineering Contradiction:

Improvetreatment simplicityVSAvoidgene delivery efficiency

Core Design Contradiction:

Ease of manufactureVSProductivity

Solution Approach 1:

The patent uses adeno-associated virus (AAV) vectors as intermediary carriers to deliver the DFNB59 gene to inner ear cells. The AAV vector acts as a mediator between the gene therapy approach and the target cells, significantly improving transduction efficiency while maintaining treatment feasibility through intracochlear injection

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If the DFNB59 gene with G292R mutation is delivered via AAV vector, then auditory nerve signaling is restored, but the device complexity increases

Engineering Contradiction:

Improveauditory nerve signalingVSAvoidgene therapy construct complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The gene therapy construct is segmented into distinct functional modules: the DFNB59 cDNA sequence encoding pejvakin, the G292R mutation site, AAV vector components (capsid, promoter, ITRs), and regulatory elements. This modular segmentation allows for systematic optimization of each component while maintaining overall functionality

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The AAV vector serves as an intermediary that simplifies the delivery mechanism by encapsulating the complex gene construct and providing targeted delivery to inner ear cells through natural viral tropism, reducing the need for complex delivery apparatus

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If AAV vector with DFNB59 gene is used to treat ANSD, then hearing and vestibular functions improve, but the treatment cost increases

Engineering Contradiction:

Improvehearing and vestibular functionVSAvoidtreatment cost

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The AAV vector system is engineered to be self-replicating and self-directed within the inner ear tissue. The virus naturally targets and infects relevant cell types (hair cells, spiral ganglion neurons) without requiring complex external guidance systems, reducing manufacturing and delivery costs while maintaining high efficacy

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS12491223B2Method for treating an auditory neuropathy spectrum disorder

Publication Date: 2025.12.09 AKOUOS INC

AI summary

The present invention provides a method for treating an auditory neuropathy spectrum disorder in a subject comprising transferring the gene of DFNB59 via an adeno-associated virus (AAV) vector to the subject.