Variant AAV Capsids for Retina and Trabecular Meshwork Transduction

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Solution Overview

Problem

Existing adeno-associated dependoparvoviruses (AAVs) face challenges in achieving efficient ocular transduction, particularly in delivering payloads to specific tissues within the eye, such as the retina and trabecular meshwork, with current vectors exhibiting low transduction efficiency.

Innovation Solution

Development of variant capsid polypeptides, including mutations at specific positions within the VP1 sequence, enhancing the ocular transduction capabilities of AAVs by improving their ability to target and deliver payloads to ocular tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If wild-type AAV capsid is used, then the virus can be produced and delivered, but the ocular transduction efficiency is low

Engineering Contradiction:

Improveocular transduction efficiencyVSAvoiddelivery effectiveness to ocular tissues

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by introducing specific amino acid mutations at positions 545-600 in the VP1 capsid sequence. These mutations alter the physical-chemical properties of the capsid surface, enabling improved interaction with ocular tissues and significantly enhancing transduction efficiency compared to wild-type AAV

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention applies local quality by making targeted mutations at specific positions (545-600) within the VP1 sequence rather than modifying the entire capsid. This localized modification approach allows the virus to maintain overall structural integrity while gaining enhanced ocular targeting capabilities at specific interaction sites

Inventive Principle:

Principle #3Local quality

2Productivity

If capsid mutations are introduced to improve ocular targeting, then transduction efficiency increases, but the complexity of producing the variant virus increases

Engineering Contradiction:

Improvetransduction efficiency in retina and trabecular meshworkVSAvoidvirus production complexity

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The patent utilizes parameter changes through site-directed mutagenesis of the capsid gene, introducing specific amino acid substitutions at positions 545-600 in the VP1 sequence. This approach allows for precise modification of viral properties while maintaining a relatively simple production workflow compared to more complex viral vector engineering approaches

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250352671A1Capsid variants and methods of using the same

Publication Date: 2025.11.20 DYNO THERAPEUTICS INC

AI summary

The disclosure is directed in part to variant capsid polypeptides that can be used to deliver payloads.