Recombinant AAV Capsids for Immune Evasion and Tissue Tropism

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Solution Overview

Problem

Current methods for isolating adeno-associated virus (AAV) genomes and capsid coding sequences are hindered by preexisting immunity and restricted tissue tropism, and traditional techniques can introduce polymerase misincorporation errors, leading to artificial recombinants.

Innovation Solution

Development of recombinant AAVs with specific capsid proteins, such as AAVrh94, AAVrh95, and others, which are deamidated at specific positions, and a method called AAV-SGA for precise isolation and sequencing of single AAV genomes, enabling efficient gene transfer and overcoming tissue tropism limitations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional polymerase chain reaction-based and cloning-based techniques are used to isolate AAV genomes, then viral genomes can be amplified and isolated, but polymerase misincorporation errors and artificial recombinants are introduced

Engineering Contradiction:

Improveisolation accuracy of AAV genomesVSAvoidaccuracy of capsid coding sequence

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent extracts and sequences complete AAV genomes and capsid coding sequences directly from viral particles without using PCR amplification. This extraction approach eliminates polymerase misincorporation errors and artificial recombinants by obtaining the genuine viral sequences directly from the virus particles themselves.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses next-generation sequencing technology as an intermediary to read the complete viral genome sequences directly from purified AAV particles. This intermediary technology replaces the error-prone PCR process with direct sequencing, providing accurate capsid coding sequences without amplification artifacts.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Duration of action of moving object

If existing AAV vectors are used for gene therapy, then long-term gene expression is achieved, but preexisting immunity and restricted tissue tropism hinder effectiveness

Engineering Contradiction:

Improvelong-term gene expressionVSAvoidtissue tropism and immune compatibility

Core Design Contradiction:

Duration of action of moving objectVSAdaptability or versatility

Solution Approach 1:

The patent systematically modifies capsid protein parameters (amino acid sequences, glycosylation patterns, deamidation states) to create AAV capsids with novel properties. These parameter changes enable the virus to evade preexisting immunity and achieve tissue tropism in previously inaccessible organs while maintaining long-term gene expression capability.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite capsid structures combining elements from different AAV serotypes and incorporating post-translational modifications (deamidation, glycosylation). This composite approach generates capsids with enhanced versatility for different tissues and immune environments while preserving the ability to provide long-term gene expression.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20260021205A1Recombinant AAV having AAV clade d and clade e capsids and compositions containing same

Publication Date: 2026.01.22 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

AI summary

Novel AAV capsids and recombinant AAV vectors comprising the same are provided.