Renal Artery Catheter Delivery of Viral Vectors to Glomeruli
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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 most molecular therapies being prevented by the permselectivity of the glomerulus and conventional intravenous or direct kidney injection methods failing to effectively treat diseases like Alport syndrome.
Innovation Solution
A minimally invasive method involving direct renal artery injection of a viral vector using a catheter, which does not require occluding the renal vein or clamping the renal artery or aorta, allowing for improved delivery and increased transgene expression in glomeruli and podocytes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional intravenous delivery is used, then the delivery method is simple and non-invasive, but the permselectivity of the glomerulus prevents entry of most molecular therapies 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. The catheter serves as a mechanical intermediary to transport the vector through the arterial system directly to the target organ, resolving the contradiction between ease of administration and delivery efficiency.
2Reliability
If direct kidney injection methods are used, then gene delivery efficiency improves, but the procedure becomes more invasive and efficiency remains inconsistent
Solution Approach 1:
The patent segments the delivery procedure into two parts: (1) percutaneous catheter insertion through a blood vessel, and (2) navigation to the renal artery for vector injection. This segmentation allows the procedure to be less invasive than direct kidney puncture while maintaining high delivery efficiency through targeted arterial injection.
Solution Approach 2:
The patent changes the delivery parameter from direct tissue injection to intravascular injection through the renal artery. This parameter change maintains high gene delivery efficiency while reducing procedural invasiveness, as the catheter is inserted through a blood vessel rather than directly penetrating the kidney tissue.
3Reliability
If direct renal artery injection is used, then transgene expression in glomeruli and podocytes increases markedly, but the procedure requires renal artery access
Solution Approach 1:
The patent uses a catheter, a universal medical device already employed in various interventional procedures, to deliver the viral vector. This multi-functional device can be inserted through standard percutaneous access and navigated to the renal artery, making the procedure accessible with existing medical technology while achieving high 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.