AAV Vector Gene Therapy for Diabetic Kidney Disease

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current gene therapy approaches for diabetic kidney disease (DKD) face challenges in efficiently targeting and maintaining continuous local expression of VEGFC within the kidney, particularly in the glomerulus, due to rapid inactivation of systemic delivery methods.

Innovation Solution

Development of an adeno-associated virus (AAV) vector gene therapy using VEGFC transgene combined with minimal nephrin promoter NPHS1 or podocin promoter NPHS2 to specifically target podocytes within the glomerulus, utilizing AAV serotypes such as 2/9, LK03, and 3B for efficient and stable transduction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If systemic delivery of VEGFC is used, then therapeutic coverage is achieved, but the vector is rapidly inactivated leading to low infection efficiency

Engineering Contradiction:

Improvetherapeutic coverageVSAvoidinfection efficiency

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent applies local quality by switching from systemic delivery to targeted delivery specifically to the kidney glomerulus. The AAV vector is designed to accumulate locally in the glomerular tissue, ensuring high concentration of the therapeutic agent at the target site while avoiding rapid systemic inactivation. This localized approach maintains both therapeutic coverage and infection efficiency.

Inventive Principle:

Principle #3Local quality

2Adaptability or versatility

If VEGFC is delivered systemically, then broad therapeutic potential is achieved, but continuous local expression cannot be maintained

Engineering Contradiction:

Improvetherapeutic potentialVSAvoidcontinuous local expression

Core Design Contradiction:

Adaptability or versatilityVSDuration of action of stationary object

Solution Approach 1:

The patent employs preliminary action by using AAV vectors that are pre-engineered with kidney-specific promoters (nephrin or podocin promoters) and targeting peptides. These vectors are designed in advance to specifically recognize and bind to kidney glomerular cells, ensuring that upon administration, they automatically localize and establish continuous local VEGFC expression without requiring repeated systemic dosing. This preliminary design ensures both broad therapeutic potential and sustained local expression.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If targeted delivery to kidney glomerulus is implemented, then local expression is maintained, but delivery complexity increases

Engineering Contradiction:

Improvecontinuous local expressionVSAvoiddelivery system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses intermediary elements to simplify the delivery system. Specifically, it employs AAV vectors that carry kidney-specific promoters (nephrin or podocin promoters) and targeting peptides as intermediaries between the VEGFC gene and the kidney glomerular cells. These intermediaries enable automatic targeting and localized expression without requiring complex external delivery infrastructure, thus maintaining reliable local expression while minimizing delivery system complexity.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20230101788A1Gene therapy

Publication Date: 2023.03.30 UNIV OF BRISTOL

AI summary

The present invention provides an adeno-associated virus (AAV) vector gene therapy comprising a vascular endothelial growth factor (VEGF)C transgene; and minimal nephrin promoter NPHS1 or podocin promoter NPHS2. The gene therapy vector can be used to target podocytes within the glomerulus of the kidney in order to treat or prevent kidney disease, such as diabetic kidney disease.