AAV Capsid VP1 Mutations for Tissue-Targeted Gene Delivery

Solution Overview

Problem

There is a need to improve the delivery efficiency, tissue targeting, and payload packaging of adeno-associated virus (AAV) vectors for gene delivery.

Innovation Solution

Engineering viral vectors with capsid polypeptide mutations in the region corresponding to amino acids 561-588, specifically altering the tropism and packaging properties of AAV vectors to enhance tissue targeting and delivery efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If wild-type AAV capsid polypeptide is used, then the viral vector has natural tropism and basic delivery capability, but the tissue targeting precision and delivery efficiency are insufficient

Engineering Contradiction:

Improvetissue targeting precisionVSAvoidcapsid polypeptide structure

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies local quality by introducing specific amino acid mutations at targeted positions (561-588) within the capsid polypeptide structure. These localized mutations modify the tropism and tissue targeting properties of the AAV vector without altering the entire capsid structure, thereby improving tissue targeting precision while maintaining overall structural integrity and minimizing complexity increases

Inventive Principle:

Principle #3Local quality

2Productivity

If capsid polypeptide mutations are introduced to modify tropism, then tissue targeting and delivery efficiency are improved, but the structural complexity and engineering difficulty increase

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidcapsid polypeptide structure

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent employs parameter changes by systematically varying amino acid sequences at specific positions (561-588) of the capsid polypeptide. Through controlled mutagenesis and selection of variants with optimized parameters, the invention achieves improved delivery efficiency and tissue targeting while managing structural complexity through focused, rather than global, modifications

Inventive Principle:

Principle #35Parameter changes

3Reliability

If capsid polypeptide mutations are introduced to modify tropism, then tissue targeting and delivery efficiency are improved, but the engineering complexity and manufacturing difficulty increase

Engineering Contradiction:

Improvepayload packagingVSAvoidvector production

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies local quality by introducing specific amino acid mutations at targeted positions (561-588) within the capsid polypeptide structure. These localized mutations modify the tropism and tissue targeting properties of the AAV vector without altering the entire capsid structure, thereby improving tissue targeting precision while maintaining overall structural integrity and minimizing complexity increases

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS12606847B2Engineered viral capsid polypeptides and uses thereof

Publication Date: 2026.04.21 PRESIDENT & FELLOWS OF HARVARD COLLEGE

AI summary

The technology described herein provides variant adeno-associated viral capsid polypeptides and viruses comprising the same. Further provided herein are methods for delivering a viral payload using viruses comprising variant capsid polypeptides described herein. Described herein are viral vectors comprising a variant sequence of the capsid gene, VP1. In particular, viral vectors with capsid polypeptide mutations that modify tropism of the viral particles relative to particles with wild-type capsid polypeptide are described.