Renal Artery Viral Vector Delivery for Targeted Glomerular Gene Transfer
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Solution Overview
Problem
Existing methods for delivering viral vectors to glomerular cells, such as podocytes, in the kidney are inefficient and often result in inconsistent gene delivery, with conventional intravenous and direct kidney injection techniques failing to effectively target these cells due to the permselectivity of the glomerulus and high risk of systemic spread.
Innovation Solution
A minimally invasive direct renal artery injection method using a catheter to deliver viral vectors, which includes inserting the catheter into the renal artery, optionally occluding the artery, and infusing the vector under no flow conditions, thereby enhancing localized transgene expression in glomeruli and podocytes while minimizing expression in other tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional intravenous delivery is used, then the procedure is simple and minimally invasive, but the gene delivery efficiency is low due to permselectivity of the glomerulus preventing entry of molecular therapies from blood into the kidney
Solution Approach 1:
The patent uses the renal artery as an intermediary pathway to deliver viral vectors directly to the kidney, bypassing the glomerular filtration barrier that blocks intravenous delivery. By injecting the viral vector into the renal artery, the therapy reaches the kidney tissue through blood flow without being filtered out by the glomerulus, thus resolving the contradiction between ease of administration and delivery efficiency
2Productivity
If direct kidney injection methods are used, then gene delivery efficiency improves, but the procedure becomes more complex and safety concerns increase
Solution Approach 1:
The patent segments the delivery procedure into two distinct parts: (1) catheter insertion into the renal artery through a percutaneous approach, and (2) viral vector injection through the catheter. This segmentation allows the complex task of direct kidney delivery to be broken down into manageable steps that can be performed with standard interventional radiology equipment, reducing overall procedural complexity while maintaining high delivery efficiency
3Reliability
If direct kidney injection is used, then transgene expression increases, but safety concerns arise from potential tissue damage and inconsistent delivery
Solution Approach 1:
The patent performs preliminary actions to ensure safe and consistent delivery: (1) The catheter is carefully navigated to the renal artery under imaging guidance before injection, ensuring proper positioning; (2) The viral vector formulation is prepared in advance with appropriate volume and concentration; (3) The injection parameters (volume, concentration, duration) are predetermined based on preclinical data. These preliminary actions reduce variability and minimize tissue damage while ensuring consistent transgene expression
Data Source
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AI summary
The present invention relates to a method of delivering a viral vector to a subject's kidney, the method comprising: (a) inserting a catheter into the renal artery; (b) optionally inflating a balloon to occlude the renal artery; and (c) injecting or infusing the viral vector into the renal artery via the catheter. The present invention also relates to a viral vector for use in therapy, wherein the viral vector is delivered by said method.