Loco-regional perfusion of a kidney
AssigneeDiNAQOR AG
InventorsÉduard AYUSO LÓPEZ, Josef EL ANDARI, Mark DEHDASHTIAN
Life of this patent
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Abstract
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.
Claims23
A method of performing localized delivery of a polynucleotide sequence to renal cells in a kidney of a mammalian subject, the method comprising:
- positioning at least one perfusion catheter in the renal artery of the kidney;
- positioning at least one recovery catheter in the renal vein of the kidney, wherein the at least one perfusion catheter and the at least one recovery catheter together with a membrane oxygenation device form a closed perfusion circuit through the kidney;
- and
- causing a perfusate to flow through the closed circuit, wherein the perfusate comprises the polynucleotide sequence packaged in an adeno-associated virus (AAV) vector, wherein the AAV vector comprises an AAV5 capsid protein, and wherein the closed circuit substantially isolates perfusion through the kidney from the systemic circulation of the subject.
4-6. (canceled)
11-21. (canceled)
A system for performing loco-regional perfusion of a kidney of a patient when fluidly coupled thereto, the system comprising:
- at least one perfusion catheter adapted for insertion into the renal artery of the kidney;
- at least one recovery catheter adapted for insertion into the renal vein of the kidney;
- a membrane oxygenation device adapted to fluidly couple to the at least one perfusion catheter, the at least one recovery catheter, and an oxygen source, wherein the at least one perfusion catheter, the at least one recovery catheter, and the membrane oxygenation device together are adapted to form a closed circuit through the kidney that is isolated from the patient's systemic circulation when the at least one perfusion catheter is inserted into the renal artery and the at least one recovery catheter is inserted into the renal vein;
- a reservoir comprising a perfusate, the perfusate comprising a polynucleotide sequence packaged in an adeno-associated virus (AAV) vector;
- and
- a pump configured to drive flow of the perfusate through the at least one perfusion catheter and the at least one recovery catheter.
A system for performing loco-regional perfusion of a kidney of a patient comprising:
- at least one perfusion catheter inserted into the renal artery of the kidney;
- at least one recovery catheter inserted into the renal vein of the kidney;
- and
- a membrane oxygenation device fluidly coupled to the at least one perfusion catheter, the at least one recovery catheter, and an oxygen source, wherein the at least one perfusion catheter, the at least one recovery catheter, and the membrane oxygenation device together with the kidney form a closed circuit through the kidney that is isolated from the patient's systemic circulation;
- a reservoir comprising a perfusate, the perfusate comprising a polynucleotide sequence packaged in an adeno-associated virus (AAV) vector;
- and
- a pump configured to drive flow of the perfusate into the kidney via the at least one perfusion catheter and out of the kidney via the at least one recovery catheter.
(canceled)
A gene therapy vector adapted for transduction renal cells of a human subject, the gene therapy vector comprising:
- an adeno-associated virus (AAV) vector comprising an AAV5 capsid protein;
- and
- a polynucleotide sequence packaged in the AAV vector.
A method of screening AAV serotypes to identify a lead serotype for use in localized gene delivery to an organ type, the method comprising:
- identifying a plurality of AAV vector candidates, each AAV vector candidate corresponding to a different AAV serotype;
- producing a perfusate composition comprising each of the plurality of AAV vector candidates each comprising a polynucleotide packaged therein;
- and
- performing localized transduction of tissue in an organ of the organ type in an animal by producing a closed circuit in the vasculature of the target organ through which the perfusate composition is circulated;
- and
- selecting, as the lead serotype, the serotype of the AAV vector candidate having the highest biodistribution of vector genome and/or the greatest RNA/protein expression in the organ compared to the remaining AAV vector candidates.
Dependencies are inferred from the claim text.