Retrograde Coronary Sinus Gene Delivery for Broad Cardiac Transduction

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Solution Overview

Problem

Existing gene therapy approaches for dilated cardiomyopathy (DCM) have not successfully corrected gene expression in the heart, raising questions about the feasibility of using viral vectors for cardiac transduction.

Innovation Solution

Retrograde coronary venous or sinus delivery of a recombinant adeno-associated virus (rAAV) vector, such as AAV2/9 capsid, is used to administer therapeutic agents like BAG3 to the heart, either with or without occluding the left main coronary artery, utilizing selective catheterization techniques.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If antegrade delivery via left coronary artery is used, then delivery to heart is achieved, but delivery efficiency and transduction breadth are limited

Engineering Contradiction:

Improvedelivery efficiencyVSAvoiddelivery route complexity

Core Design Contradiction:

ProductivityVSEase of operation

Solution Approach 1:

The patent inverts the conventional antegrade delivery approach by using retrograde delivery through the coronary sinus and great cardiac vein. This reversal enables the therapeutic to reach the heart muscle more effectively, achieving broader transduction and improved delivery efficiency while maintaining procedural feasibility through established catheterization techniques

Inventive Principle:

Principle #13The other way round (Inversion)

2Reliability

If retrograde delivery via coronary sinus is used, then gene transduction efficiency is improved, but procedural complexity increases

Engineering Contradiction:

Improvetransduction efficiencyVSAvoidcatheterization complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs the coronary sinus and great cardiac vein as intermediary pathways to deliver the therapeutic to the heart. These natural vascular structures serve as mediators that facilitate retrograde delivery, enabling efficient transduction while utilizing existing anatomical pathways to minimize procedural complexity

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If therapeutic delivery to heart is achieved, then cardiac function improves, but risk of ischemia/reperfusion injury increases

Engineering Contradiction:

Improvecardiac function improvementVSAvoidischemia/reperfusion injury risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent performs preliminary occlusion of the left main coronary artery or selective occlusion of antegrade flow before retrograde delivery. This preliminary action creates a controlled environment that directs the therapeutic to the heart muscle while managing ischemia/reperfusion risk through planned, controlled occlusion rather than uncontrolled ischemic events

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20260069719A1Retrograde coronary venous or sinus administration of therapeutics

Publication Date: 2026.03.12 RENOVACOR INC

AI summary

The invention provides methods of delivering a therapeutic to the heart. In one embodiment, a method includes administering to a subject the therapeutic via retrograde coronary venous or sinus delivery thereby delivering the therapeutic to the heart.