CpG-Reduced AAV Vector Composition for Low-Immunogenic Payload Delivery

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Solution Overview

Problem

Existing adeno-associated viral (AAV) vectors face challenges in delivering therapeutic payloads with high efficacy and low immunogenicity, particularly in treating cancers like glioblastoma, due to high CpG dinucleotide content leading to immune activation.

Innovation Solution

Recombinant AAV vectors with reduced or depleted CpG dinucleotides and increased methylation, combined with a CAG promoter and WPRE sequence, to enhance therapeutic efficacy and minimize immunogenicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If AAV vectors use standard coding sequences with normal CpG dinucleotide content, then the vectors can deliver therapeutic payloads effectively, but the high CpG content triggers immune activation and increases immunogenicity

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidimmune activation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the coding sequence by changing CpG dinucleotides to TpG or CpA dinucleotides, altering the nucleotide composition parameter to reduce immunogenicity while preserving protein coding function. This parameter change resolves the contradiction by lowering immune activation without sacrificing therapeutic delivery capability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent converts the harmful effect of CpG dinucleotides (immune activation) into a beneficial feature by strategically replacing them with alternative dinucleotides. The modified coding sequence maintains therapeutic function while eliminating the harmful immune response, effectively turning a problematic element into an improved design

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Productivity

If AAV vectors deliver therapeutic payloads with high potency, then treatment effectiveness improves, but systemic toxicity increases

Engineering Contradiction:

Improvetherapeutic potencyVSAvoidsystemic toxicity

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent employs tissue-specific promoters (e.g., GFAP for astrocytes, Syn for neurons) to drive expression of the therapeutic payload only in target cells within the central nervous system. This localizes the therapeutic effect to the desired tissue while minimizing systemic exposure and toxicity, resolving the contradiction between potency and safety

Inventive Principle:

Principle #3Local quality

3Productivity

If AAV vectors use strong promoters to drive high-level payload expression, then therapeutic efficacy increases, but immunogenicity and immune response increase

Engineering Contradiction:

Improvepayload expression levelVSAvoidimmunogenicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies promoter sequences by removing or reducing CpG dinucleotide content while maintaining promoter strength and tissue-specificity. This parameter change allows the promoter to drive high-level expression without triggering immune activation, resolving the contradiction between expression level and immunogenicity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent converts the potentially harmful CpG-containing promoter sequences into beneficial CpG-reduced or CpG-free promoter variants that maintain transcriptional activity. The modified promoters drive robust payload expression while avoiding immune recognition, turning a harmful element into an improved component

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20260035717A1Adeno-associated viral vector compositions and methods of use

Publication Date: 2026.02.05 SIREN BIOTECHNOLOGY INC

AI summary

Described herein are nucleic acids and recombinant viral vectors comprising said nucleic acids, wherein said nucleic acids encode a payload of interest (e.g., an interferon).