Renal Closed-Loop Perfusion for Targeted AAV Kidney Delivery
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Solution Overview
Problem
Existing gene and cell therapy techniques for renal conditions face challenges in achieving targeted, homogeneous, and minimally invasive delivery of therapeutic agents to the kidney, with issues related to vector efficiency, dose, specificity, and safety.
Innovation Solution
A method involving a closed perfusion circuit using a perfusion catheter and a recovery catheter, combined with a membrane oxygenation device, delivers a polynucleotide sequence packaged in an AAV vector through the renal artery and vein, maintaining high concentration and isolating perfusion from systemic circulation to enhance delivery efficiency and minimize leakage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If a polynucleotide sequence is delivered via systemic circulation, then the therapeutic agent reaches the kidney, but the delivery lacks target specificity and results in low vector efficiency at the renal site
Solution Approach 1:
The patent segments the systemic circulation into a localized renal perfusion circuit by inserting catheters into the renal artery and vein, creating a separate closed-loop system that isolates and concentrates the therapeutic agent specifically at the kidney site, thereby achieving both high specificity and high local concentration
Solution Approach 2:
The patent applies local quality by maintaining high concentration of the AAV vector (at least about 5×10^7 vector genomes per mL of plasma) specifically within the renal perfusion circuit, while the rest of the systemic circulation receives minimal or no exposure, optimizing therapeutic effect at the target organ
2Reliability
If a high dose of AAV vector is administered to ensure sufficient delivery to renal cells, then treatment efficacy improves, but leakage into systemic circulation increases causing safety concerns
Solution Approach 1:
The patent extracts the therapeutic agent delivery from the general systemic circulation and confines it to a dedicated renal perfusion circuit, removing the harmful aspect of widespread systemic distribution while preserving the beneficial high-dose delivery to renal cells
Solution Approach 2:
The patent introduces a closed perfusion circuit with membrane oxygenation device as an intermediary system between the AAV vector and the kidney, allowing controlled high-concentration delivery while the circuit itself contains and recycles the vector, preventing direct leakage into systemic circulation
3Ease of operation
If conventional gene therapy delivery methods are used, then the procedure is simple, but the delivery is not homogeneous and vector efficiency is low
Solution Approach 1:
The patent creates a multi-functional system where the perfusion circuit simultaneously achieves homogeneous distribution, high concentration maintenance, and controlled delivery duration (30-90 minutes), combining multiple delivery advantages in a single integrated approach while remaining minimally invasive
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 method achieves localized delivery of therapeutic agents with high vector genome copy numbers in renal cells while minimizing systemic leakage, thereby improving treatment efficacy and safety.
Implementation Method 1
a membrane oxygenation device form a closed perfusion circuit through the kidney
Data Source
AI summary
Disclosed is a method for treating a renal condition by loco-regional perfusion of one or both of a patient's kidneys. A closed circuit may be formed with a perfusion catheter positioned in the renal artery of the kidney, a recovery catheter positioned in the renal vein of the kidney, and an external membrane oxygenator disposed therebetween. A perfusate containing, for example, a drug may be circulated through the closed circuit while isolating the closed circuit from the patient's systemic circulation.