Localized Liver Gene Therapy Delivery With Balloon Catheters
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Solution Overview
Problem
Current gene therapy delivery methods for large mammals are inefficient, costly, and trigger immune responses due to systemic injection of large virus vector doses, which is impractical and ineffective for treating genetic diseases like diabetes, cystic fibrosis, and hemophilia.
Innovation Solution
A localized liver gene therapy system using inflatable balloon catheters to contain viral vectors within blood vessels, combined with electrodes for electroporation, enhances vector uptake in hepatic cells with reduced doses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If systemic injection of large virus vector doses is used to treat large mammals, then the necessary amount of hepatocytes can be converted for effective therapy, but the treatment becomes cost-prohibitive and triggers adaptive immunity that destroys virus and genetically modified cells
Solution Approach 1:
The patent applies local quality by delivering gene vectors directly to the liver through catheterization of the hepatic artery or portal vein, rather than systemic injection. This localized delivery concentrates the vector dose at the target site, achieving effective transduction of hepatocytes while minimizing exposure to the rest of the body, thereby reducing immune response and cost.
Solution Approach 2:
The patent uses an intermediary delivery system consisting of a catheter and delivery device that transports the gene vector directly to the liver. This intermediary mechanism enables precise localization of the vector to the target organ, avoiding the need for high systemic doses and the associated immune reactions and costs.
2Productivity
If large doses of virus vectors are injected systemically, then sufficient hepatocytes can be transduced in large mammals, but the expense of producing and injecting such large amounts becomes impractical
Solution Approach 1:
The patent implements local quality by directing the gene vector through a catheter directly into the hepatic artery or portal vein, ensuring concentrated delivery to the liver. This localized approach achieves effective gene transduction in large mammals using much smaller vector doses compared to systemic injection, making the treatment economically feasible.
Solution Approach 2:
The patent segments the delivery process by using a catheter-based system that divides the body into treated (liver) and untreated regions. This segmentation allows the vector to be delivered precisely where needed, reducing the total quantity required while maintaining effective gene delivery to hepatocytes.
3Ease of operation
If systemic injection is used for gene delivery, then functional genes can be delivered via the circulatory system, but the vectors are diluted systemically reducing local concentration and uptake efficiency
Solution Approach 1:
The patent applies local quality by using a catheter to deliver the gene vector directly to the liver's blood vessels (hepatic artery or portal vein). This method maintains high local concentration of the vector at the target site, preventing systemic dilution and maximizing uptake efficiency by hepatocytes, while still being operationally simple.
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
This method improves transduction efficiency and reduces immune reactions by concentrating viral vectors locally, allowing effective gene delivery with lower doses and minimizing systemic waste.
Implementation Method 1
A localized liver gene therapy system using inflatable balloon catheters to contain viral vectors within blood vessels
Implementation Method 2
electrodes in adjacent blood vessels are used to produce electroporation in the tissue region between the electrodes offsetting this localization of delivery and improving uptake of the vector
Data Source
AI summary
A “localizable” systemic gene therapy system is provided substantially increasing the transfection efficiency of the gene vectors into targeted tissue cells and substantially reducing the escape of the gene vectors from the targeted tissue volume, such as would waste the vectors, promote undesired immune reactions, and/or incur prohibitive costs for the required dose of gene-containing virus vectors. In this regard, the invention provides a means to simultaneously achieve local electroporation and gene-containing vector injection in a portion of a vascularized organ. It includes two double-balloon catheters that create contained volumes in parallel blood vessels for the introduction of vectors with reduced loss along with electrodes providing electroporation of the cells in the same location where the vectors are injected.