Anc80 AAV Vector for Inner Ear Gene Delivery

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Solution Overview

Problem

Current gene therapy approaches for hearing loss face challenges in efficiently and safely delivering nucleic acids to inner ear cells, particularly inner and outer hair cells, due to low transduction rates and potential toxicity, limiting the effectiveness of cochlear gene therapy.

Innovation Solution

The use of an adeno-associated virus (AAV) vector containing an ancestral AAV capsid protein, such as Anc80, which efficiently targets and transduces inner ear cells, including inner and outer hair cells, and other cell types, enabling high transduction rates and safety profiles, facilitating the delivery of various transgenes to restore hearing and vestibular function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional AAV vectors are used for gene delivery to inner ear cells, then the delivery method is established and safe, but the transduction rate is low and efficiency is poor

Engineering Contradiction:

Improvetransduction rateVSAvoidsafety profile

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent changes the capsid protein parameter of the AAV vector by using an ancestral AAV capsid (Anc80) instead of conventional AAV capsids. This parameter change results in dramatically improved transduction rates in inner ear cells while maintaining a safe profile, resolving the contradiction between low transduction efficiency and safety concerns

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite viral vector system by combining the ancestral AAV capsid (Anc80) with conventional AAV genetic elements (rep, ITRs, and transgene). This composite approach leverages the superior cell targeting capabilities of the ancestral capsid while maintaining the proven safety and functionality of conventional AAV vector components

Inventive Principle:

Principle #40Composite materials

2Productivity

If higher transduction rates are achieved in inner ear cells, then gene delivery efficiency improves, but potential toxicity increases

Engineering Contradiction:

Improvegene delivery efficiencyVSAvoidtoxicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

By changing the capsid protein parameter to the ancestral Anc80 variant, the patent achieves high transduction rates in inner ear cells without the toxicity concerns associated with other high-efficiency delivery methods. The ancestral capsid naturally exhibits tropism for inner ear cells at high efficiency while maintaining biocompatibility

Inventive Principle:

Principle #35Parameter changes

3Productivity

If conventional AAV vectors are used, then the delivery system is well-characterized, but antigenic similarity leads to immune recognition and reduced efficacy

Engineering Contradiction:

Improvetransduction efficiencyVSAvoidantigenic distinctness

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

Instead of using conventional AAV capsids that are well-studied but immunogenic, the patent inverts the approach by using an ancestral AAV capsid (Anc80) that has been evolutionarily distant from modern AAVs. This inversion provides antigenic distinctness that avoids pre-existing immunity while the vector remains based on the proven AAV platform

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent changes the capsid antigenicity parameter by selecting an ancestral AAV capsid sequence that is genetically distinct from conventional AAV serotypes. This parameter change reduces recognition by pre-existing neutralizing antibodies while maintaining the ability to deliver therapeutic genes to inner ear cells

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12102692B2Materials and methods for delivering nucleic acids to cochlear and vestibular cells

Publication Date: 2024.10.01 CHILDRENS MEDICAL CENT CORP

AI summary

Provided herein are materials and methods for efficiently delivering nucleic acids to cochlear and vestibular cells.