Hydrodynamic Gene Delivery via Biliary Tree
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Solution Overview
Problem
Current methods for liver-targeted gene therapy lack a simple, safe, and efficient delivery system for nucleic acids, often resulting in fatal complications and side effects due to the delivery vehicle and method, hindering effective treatment of liver-related diseases.
Innovation Solution
Intra-biliary delivery of nucleic acids via hydrodynamic administration, using elevated pressure to deliver a nucleic acid expression cassette into the biliary tree, liver, or pancreas, with real-time pressure measurement and modification to ensure effective transfection of cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional liver-targeted gene therapy delivery methods are used, then gene delivery can be achieved, but fatal complications and side effects occur due to the delivery vehicle and method
Solution Approach 1:
The patent extracts and eliminates the harmful delivery vehicle (viral vectors, liposomes, polymers) from the gene therapy system, using only naked plasmid DNA as the genetic material. This removes the source of fatal complications and side effects while maintaining the therapeutic function through alternative delivery routes (intravenous, intraportal, intrahepatic injection) that do not require toxic carriers.
2Reliability
If a simple and safe gene delivery method is used, then safety is improved, but delivery efficiency and transfection effectiveness decrease
Solution Approach 1:
The patent applies local quality by directing the gene delivery to specific liver regions through targeted injection methods (intraportal injection for portal vein delivery, intrahepatic injection for direct liver parenchyma delivery). This localized approach ensures high transfection efficiency in the target area while maintaining safety by avoiding systemic distribution and reducing off-target effects.
Solution Approach 2:
The patent uses the biliary tree and hepatic sinusoids as intermediary pathways to deliver naked plasmid DNA to hepatocytes. These natural anatomical structures serve as conduits that facilitate efficient gene delivery without requiring exogenous delivery vehicles, thereby maintaining both safety and transfection effectiveness.
3Productivity
If viral vectors are used for gene delivery, then transfection efficiency is improved, but immunogenicity and toxicity increase
Solution Approach 1:
The patent completely removes viral vectors from the delivery system, using only non-viral naked plasmid DNA. This extraction eliminates the immunogenicity and toxicity associated with viral proteins and genetic material while achieving sufficient transfection efficiency through optimized physical delivery methods and utilization of natural hepatic uptake pathways.
Solution Approach 2:
The patent employs simple, non-persistent naked plasmid DNA molecules as the delivery vehicle instead of complex, potentially persistent viral vectors. These disposable plasmid molecules are degraded after delivering their genetic payload, avoiding long-term immunogenicity and toxicity issues while providing adequate transient gene expression for therapeutic effect.
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 approach provides a minimally invasive, safe, and efficient method for gene therapy, effectively transfecting liver and pancreas cells, reducing systemic toxicity and cardiovascular risks, and achieving stable expression of therapeutic proteins.
Implementation Method 1
administering at elevated pressure an effective amount of a nucleic acid expression cassette to the subject's biliary tree, liver or pancreas
Data Source
AI summary
Intrabiliary hydrodynamic injection of nucleic acid for in vivo gene therapy for treatment of liver or pancreas disease and other disorders.