Mutated Dependoparvovirus Capsids for CNS and Muscle Gene Delivery

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Solution Overview

Problem

Existing dependoparvovirus vectors, such as AAVs, face challenges in achieving efficient biodistribution and transduction in specific tissues like the central nervous system, muscle, and cardiac muscle, limiting their effectiveness in gene therapy applications.

Innovation Solution

Development of capsid polypeptides with specific mutations, including positions corresponding to Q579, Q592, T593, W595, V596, N598, and I601 in the VP1 sequence, enhancing the biodistribution and transduction efficiency of viral particles in CNS, muscle, and cardiac muscle.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing dependoparvovirus vectors are used, then viral particles can be produced and delivered to cells, but biodistribution and transduction efficiency in specific tissues (CNS, muscle, cardiac muscle) are insufficient

Engineering Contradiction:

Improvebiodistribution and transduction efficiencyVSAvoidtissue-specific targeting capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by introducing specific amino acid mutations at defined positions (Q579, Q592, T593, W595, V596, N598, I601) in the VP1 capsid polypeptide. These localized changes modify specific regions of the capsid structure to enhance interaction with tissue-specific receptors, thereby improving biodistribution and transduction efficiency in target tissues such as CNS, muscle, and cardiac muscle without altering the overall viral particle structure.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by systematically varying the amino acid sequence parameters at specific positions in the capsid polypeptide. By changing the chemical properties (charge, hydrophobicity, size) of amino acids at positions Q579, Q592, T593, W595, V596, N598, and I601, the viral particles achieve altered biodistribution patterns and enhanced transduction efficiency in specific tissues while maintaining viral assembly and basic infectivity.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If capsid polypeptides with multiple mutations are developed, then transduction efficiency in target tissues is enhanced, but the complexity of producing and characterizing the viral vectors increases

Engineering Contradiction:

Improvetransduction efficiencyVSAvoidcapsid polypeptide sequence complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the capsid optimization into discrete, manageable components: specific amino acid positions (Q579, Q592, T593, W595, V596, N598, I601) are identified and modified independently. This segmented approach allows for systematic construction of mutant capsid polypeptides and facilitates characterization of individual mutation effects on transduction efficiency, thereby reducing overall complexity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs universality by developing a standardized set of mutations that can be applied across different dependoparvovirus vector systems. The defined amino acid changes at specific positions create a universal platform for enhancing transduction efficiency in CNS, muscle, and cardiac muscle tissues that can be adapted to various viral vector backbones and payload configurations.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20260027238A1Capsid polypeptides and methods of use thereof

Publication Date: 2026.01.29 DYNO THERAPEUTICS INC

AI summary

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