Stereocilin Split-Vector Recombination for Genetic Hearing Loss

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for non-syndromic sensorineural hearing loss, which affects 70-80% of genetic deafness cases, primarily involve hearing amplification and cochlear implants, lacking effective agents or methods for preventing or reversing the condition.

Innovation Solution

A composition of at least two different nucleic acid vectors, each encoding a portion of the stereocilin protein, undergoes homologous recombination in mammalian cells to produce a full-length stereocilin protein, addressing defective genes and treating non-syndromic sensorineural hearing loss.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hearing amplification and cochlear implants are used to treat non-syndromic sensorineural hearing loss, then hearing function can be partially restored, but there is no method to prevent or reverse the underlying genetic cause of the condition

Engineering Contradiction:

Improvehearing function restorationVSAvoidability to prevent or reverse genetic condition

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The stereocilin gene is divided into multiple segments, with each nucleic acid vector containing a different segment of the gene. When these vectors are introduced into the same cell, the segments are recombined to form the complete functional gene, enabling prevention and reversal of the genetic condition while avoiding the limitations of current amplification and implant technologies

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Nucleic acid vectors serve as intermediaries to deliver gene segments into target cells. These vectors act as carriers that transport the divided gene segments to the appropriate location where they will be recombined, providing a mechanism to address the underlying genetic cause rather than just managing symptoms

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of manufacture

If a single nucleic acid vector encodes the full-length stereocilin protein, then the treatment approach is simple, but it is difficult to ensure proper expression and assembly of the protein in mammalian cells

Engineering Contradiction:

Improvesimplicity of treatment approachVSAvoidproper expression and assembly of protein

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The full-length stereocilin coding sequence is divided into multiple segments distributed across different nucleic acid vectors. This segmentation allows each vector to be smaller and easier to manufacture while ensuring that the complete protein can be properly expressed through recombination of the segments in mammalian cells

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Multiple nucleic acid vectors, each containing a segment of the stereocilin gene, are combined in the same cell. The segments merge through homologous recombination to form the complete functional gene, ensuring proper protein expression and assembly while maintaining the manufacturing advantages of smaller vector components

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If multiple nucleic acid vectors are used to encode portions of stereocilin protein, then proper gene recombination and protein expression are achieved, but the complexity of the treatment increases

Engineering Contradiction:

Improvegene recombination and protein expressionVSAvoidcomplexity of treatment

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The stereocilin gene is segmented into multiple portions, each contained in a separate nucleic acid vector. This segmentation enables reliable recombination and protein expression while the modular design actually simplifies the overall treatment approach by allowing standardized vector components to be combined in different configurations

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The nucleic acid vectors are designed with universal features that allow them to function independently as well as work together in combination. Each vector can be characterized and tested separately, but when introduced into the same cell, they automatically work together to recombine and express the complete stereocilin protein, reducing the complexity of treatment administration

Inventive Principle:

Principle #6Universality (Multi-functionality)

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

The approach increases expression of a functional stereocilin protein, potentially reversing hearing loss by restoring normal hearing levels in affected individuals.

Implementation Method 1

when introduced into a mammalian cell the at least two different vectors undergo homologous recombination with each other, thereby forming a recombined nucleic acid that encodes a full-length stereocilin protein

Methodology Applied

Scientific EffectHomologous recombination:

Data Source

PatentUS20260000787A1Methods of treating non-syndromic sensorineural hearing loss

Publication Date: 2026.01.01 AKOUOS INC

AI summary

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of a stereocilin protein, and the use of these compositions to treat non-syndromic sensorineural hearing loss in a subject.