AAV-hPGIS Gene Therapy for PAD Angiogenesis

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Solution Overview

Problem

Current therapeutic methods for peripheral arterial disease (PAD) are limited in effectiveness, particularly for critical limb ischemia, where existing treatments often fail to adequately address the need for enhanced blood vessel formation and perfusion, leading to high morbidity and mortality rates.

Innovation Solution

A method involving the administration of a composition containing adeno-associated virus (AAV) carrying a human PGIS gene that synthesizes prostaglandin I2 (PGI2), which induces the production of vascular endothelial growth factor (VEGF), promoting angiogenesis and improving blood perfusion in ischemic tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional therapeutic methods (drugs, stents, surgical bypass) are used for PAD treatment, then immediate symptom relief is achieved, but long-term effectiveness is limited and morbidity/mortality rates remain high

Engineering Contradiction:

Improvelong-term treatment effectivenessVSAvoidangiogenesis capability

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies preliminary action by introducing the hPGIS gene into target tissues before ischemic events occur or early in the disease progression. The gene transfer system establishes prostaglandin I2 production capacity in advance, creating a reservoir of angiogenic activity that can respond to ischemic conditions as they develop, rather than attempting to stimulate angiogenesis after tissue damage has occurred.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses prostaglandin I2 as an intermediary substance that mediates between the introduced hPGIS gene and the desired angiogenic outcome. The gene product (prostaglandin I2) acts as a signaling molecule that indirectly promotes VEGF production and subsequent angiogenesis, providing a controlled and sustained angiogenic response rather than direct growth factor administration.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If high doses of angiogenesis factors are administered to enhance blood vessel formation, then angiogenesis is promoted, but risk of adverse effects and tumor growth increases

Engineering Contradiction:

Improveangiogenesis rateVSAvoidadverse effects and tumor risk

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent implements self-service by enabling target tissues to autonomously produce prostaglandin I2 through the introduced hPGIS gene. The tissue itself becomes the source of the angiogenic stimulus, producing the mediator locally and continuously as needed. This eliminates the need for external administration of high-dose growth factors and their associated risks, while maintaining sufficient angiogenic activity through endogenous production.

Inventive Principle:

Principle #25Self-service

3Duration of action of stationary object

If gene therapy with hPGIS is administered to promote sustained angiogenesis, then long-term blood perfusion improvement is achieved, but treatment complexity and cost increase

Engineering Contradiction:

Improveduration of angiogenesis effectVSAvoidgene therapy delivery system

Core Design Contradiction:

Duration of action of stationary objectVSDevice complexity

Solution Approach 1:

The patent applies universality by using a broadly applicable gene transfer system that can be delivered through multiple routes (injection, viral vectors, etc.) and is suitable for various ischemic conditions. The hPGIS gene itself serves multiple functions: it produces prostaglandin I2 directly, stimulates VEGF production indirectly, and provides sustained angiogenic activity across different tissue types and disease states, reducing the need for condition-specific treatment protocols.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The approach significantly enhances blood perfusion and reduces limb necrosis rates, demonstrating a notable improvement in ischemic conditions by promoting the formation of collateral blood vessels and neovascularization, thus offering a more effective treatment for PAD.

Implementation Method 1

administering, to an individual, a composition including adeno-associated virus (AAV) carrying a hPGIS gene coding for human prostacyclin synthase (hPGIS) which synthesizes prostaglandin I2 (PGI2)

Methodology Applied

Scientific EffectGene expression:

Implementation Method 2

which induces the production of vascular endothelial growth factor (VEGF), promoting angiogenesis and improving blood perfusion in ischemic tissues

Methodology Applied

Scientific EffectSignal transduction:

Data Source

PatentUS11666615B2Method for inducing production of vascular endothelial growth factor

Publication Date: 2023.06.06 TANABE TADASHI

AI summary

The present invention relates to a method for inducing production of vascular endothelial growth factor (VEGF). The method includes administering, to an individual, a composition including adeno-associated virus (AAV) carrying a hPGIS gene coding for human prostacyclin synthase (hPGIS) which synthesizes prostaglandin I2 (PGI2).