Method of administering recombinant adeno-associated virus to kidneys

Abstract

The techniques described herein relate to methods for administering recombinant adeno-associated virus (rAAV) to a target kidney using a retrograde ureteral pathway. Such administration methods can be used to treat kidney-related disorders in subjects requiring treatment of kidney-related disorders. Pharmaceutical compositions comprising recombinant adeno-associated virus (rAAV) for administration to the kidneys are also described herein.

Claims

[Claim 1] A method for transducing nephrons in the target kidney using recombinant adeno-associated virus (rAAV), To guide a catheter through the target urethra, bladder, and ureter; and A method comprising administering a solution containing rAAV to the renal pelvis of the kidney via a catheter in a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the body weight of the subject), wherein the renal nephrons are transduced with high efficiency by rAAV. [Claim 2] The method according to claim 1, wherein a solution containing rAAV is administered to the kidney for about 0.5 minutes to about 60 minutes. [Claim 3] The method according to claim 1, wherein a solution containing rAAV is administered to the kidney for about 1 to 2 minutes. [Claim 4] A solution containing rAAV at approximately 25 cmH ２ O ~ approx. 55cmH ２ The method according to claim 1, administered at an intrarenal pressure of O. [Claim 5] The method according to claim 1, which results in transduction by rAAV of at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, or more of the nephrons in the kidney. [Claim 6] The method according to claim 1, wherein the transduction efficiency of rAAV on a nephron in a kidney is increased by at least 2, at least 5, at least 10, at least 50, at least 100, at least 400, at least 1000, or at least 3500 compared to the corresponding transduction efficiency of a corresponding nephron in another kidney treated by intravenous administration of a solution containing rAAV. [Claim 7] The method according to claim 1, wherein the rAAV does not contain an AAV9 capsid, and the transduction efficiency of the rAAV to nephrons in a kidney is increased by at least 2 times, at least 5 times, at least 10 times, at least 50 times, at least 100 times, at least 400 times, at least 1000 times, or at least 3500 times compared to the corresponding transduction efficiency achieved by administering an rAAV containing an AAV9 capsid to another kidney by the same method. [Claim 8] The method according to claim 1, wherein the rAAV does not contain an AAV9 capsid, and the transduction efficiency of the rAAV in proximal tubular cells of nephrons in a kidney is increased by at least 2 times, at least 5 times, at least 10 times, at least 50 times, at least 100 times, at least 400 times, at least 1000 times, or at least 3500 times compared to the corresponding transduction efficiency in proximal tubular cells achieved by administering an rAAV containing an AAV9 capsid to another kidney by the same method. [Claim 9] The method according to claim 1, further comprising the step of blocking the renal blood vessels of the kidney, selected from the group consisting of the renal artery, renal vein, and combinations thereof, before administering a solution containing rAAV. [Claim 10] The method according to claim 9, further comprising the step of administering a solution containing rAAV and then releasing the blockage of the renal blood vessels after a period of about 10 to about 60 minutes. [Claim 11] The method according to claim 1, wherein the kidney is not isolated from the systemic circulation. [Claim 12] The method according to claim 1, wherein a renal vessel selected from the group consisting of the renal artery, renal vein, and combinations thereof of the kidney is not blocked during the execution of the method. [Claim 13] A solution containing rAAV at approximately 27 cmH ２ O~about 80cmH ２ The method according to claim 1, wherein the drug is administered to the kidney at an intrarenal pressure of O. [Claim 14] The method according to claim 1, wherein the subject is a human, a non-human primate, a horse, a dog, or a pig. [Claim 15] The method according to claim 1, wherein at least about 30% of the kidney nephrons are transduced with rAAV. [Claim 16] The method according to claim 1, wherein the volume of the solution containing rAAV administered to the subject is approximately 0.13 mL / kg to approximately 0.33 mL / kg. [Claim 17] The method according to claim 1, wherein the volume of the solution containing rAAV administered to the subject is approximately 0.27 mL / kg to approximately 0.33 mL / mg. [Claim 18] The method according to claim 1, wherein a solution containing rAAV is administered using a balloon catheter. [Claim 19] The method according to claim 9, wherein the renal blood vessels are occluded using a balloon catheter. [Claim 20] The method according to claim 9, wherein the renal blood vessel is blocked using a clamp. [Claim 21] The method according to claim 9, wherein only one of the renal artery or the renal vein is blocked. [Claim 22] The method according to claim 1, wherein the renal vein of the kidney is not blocked. [Claim 23] The method according to claim 1, wherein continuous perfusion of an isolated kidney is not included. [Claim 24] The method according to claim 1, wherein the closed circuit does not include a kidney. [Claim 25] The method according to claim 1, wherein the system does not include a substantially closed system including a kidney. [Claim 26] The method according to claim 1, wherein the circulation is not diverted from the kidneys. [Claim 27] The method according to claim 1, wherein the procedure does not involve bypassing the kidney. [Claim 28] The method according to claim 1, performed in vivo. [Claim 29] The method according to claim 1, which is not performed by ex vivo. [Claim 30] The method according to claim 10, wherein the period for blocking at least one renal blood vessel is 15 to 45 minutes following the blocking. [Claim 31] The method according to claim 10, wherein the period for blocking at least one renal blood vessel is 20 to 40 minutes following the blocking. [Claim 32] The method according to claim 10, wherein the period for blocking at least one renal blood vessel is about 15 to 30 minutes following the blocking. [Claim 33] The method according to claim 10, wherein the volume of the solution containing rAAV is about 0.13 mL / kg to about 0.33 mL / kg, and the period for occluding the renal blood vessels is about 15 to 30 minutes following occlusion. [Claim 34] The method according to claim 1, wherein rAAV comprises an AAV capsid protein selected from Table 1. [Claim 35] The method according to claim 1, wherein rAAV comprises a capsid protein selected from the group consisting of AAV2G9, AAV2.5, AAVDJ, and AAV2. [Claim 36] The method according to claim 35, wherein the capsid protein is AAV2G9. [Claim 37] The method according to claim 1, wherein rAAV includes a field of rational multiples. [Claim 38] The solution is 10 ８ Viral genome / mL (vg / mL) ~ 10 １５ The method according to claim 1, comprising rAAV at a concentration of vg / mL. [Claim 39] The solution is 10 ８ vg / mL ~ 10 １３ The method according to claim 1, comprising rAAV at a concentration of vg / mL. [Claim 40] The method according to claim 1, wherein the solution contains a total of 1×10 １３ to 2×10 １３ of rAAV viral genomes. [Claim 41] The solution totals 5 x 10 １３ ~6 x 10 １３ The method according to claim 1, comprising the rAAV virus genome. [Claim 42] The solution totals 1 x 10 １０ The method according to claim 1, comprising the viral genome. [Claim 43] The method according to claim 1, wherein rAAV includes a transgene. [Claim 44] The introduced genes include alanine-glyoxylate aminotransferase (AGXT); infant Bartter syndrome with sensorineural hearing loss (BSND); chloride voltage-gated channel 5 (CLCN5); chloride voltage-gated channel Ka (CLCNKA); chloride voltage-gated channel Kb (CLCNKB); type IV collagen α3 chain (COL4A3); type IV collagen α4 chain (COL4A4); type IV collagen α5 chain (COL4A5); glucosidase IIα subunit (GANAB); glyoxylate and hydroxypyruvate reductase (GRHPR); hepatocyte nuclear factor 1 (HNF1) homeobox B (HNF1B); 4-hydroxy-2-oxoglutarate aldolase 1 (HOGA1); potassium inward rectifier channel subfamily J member 1 (KCNJ1); MAGED2 ( The method according to claim 43, selected from the group consisting of: type V; mucin 1 (MUC1); nephrocystin 1 (NPHP1); nephrin (NPHS1); nephrotic syndrome 2 (NPHS2; podosin); inositol polyphosphate-5-phosphatase (OCRL); polycystin 1 (PKD1); polycystin 2 (PKD2); polycystin 1 (PKHD1); protein transport protein Sec61 subunit α isoform 1 (SEC61A1); solute carrier family 12 member 1 (SLC12A1); solute carrier family 12 member 3 (SLC12A3); solute carrier family 3 member 1 (SLC3A1); solute carrier family 7 member 9 (SLC7A9); von Hippel-Lindau tumor suppressor (VHL); and combinations thereof. [Claim 45] The transgenes are: aquaporin 2 (AQP2); ATPase Na+ / K+ transport subunit alpha-1 (ATP1A1); ATPase H+ transport V0 subunit A4 (ATP6V0A4); ATPase H+ transport V1 subunit B1 (ATP6V1B1); arginine vasopressin receptor 2 (AVPR2); vertine CLCNK (chloride channel K) type accessory subunit beta (BSND); carbonic anhydrase 2 (CA2); calcium-sensing receptor (CaSR); chloride voltage-gated channel 5 (CLCN5); CLCNKA (chloride voltage-gated Existence channel Ka); Chloride voltage-gated channel Kb (CLCNKB); Claudin 16 (CLDN16); Claudin 19 (CLDN19); Cyclin and CBS domain divalent metal cation transport mediator 2 (CNNM2); Karin 3 (CUL3); Cytochrome P450 family 11 subfamily B member 1 (CYP11B1); Cytochrome P450 family 11 subfamily B member 2 (CYP11B2); Cytochrome P450 family 17 subfamily A member 1 (CYP17A1); Cytochrome P450 family Lee 21 subfamily A member 2 (CYP21A2); epidermal growth factor (EGF); epidermal growth factor receptor (EGFR); enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase (EHHADH); FAM111 (family 111) trypsin-like peptidase A (FAM111A); forkhead box I1 (FOXI1); FXYD domain / motif-containing ion transport regulator 2 (FXYD2); glycine amidinotransferase (GATM); guanine nucleotide-binding protein; alpha-stimulating (GNAS) ); Hepatocyte nuclear factor 1 (HNF1) homeobox B (HNF1B); Hepatocyte nuclear factor 4 alpha (HNF4A); Hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2); Hydroxy-delta-5-steroid dehydrogenase, 3-beta- and steroid delta-isomerase 2 (HSD3B2); Potassium voltage-gated channel subfamily A member 1 (KCNA1); Potassium inward rectifier channel subfamily J member 1 (KCNJ1); Potassium inward rectifier channel subfamily J member 10 (KCNJ10);Kelch family member 3 (KLHL3); melanoma antigen gene family member D2 (MAGED2); nuclear receptor subfamily 3 group C member 2 (NR3C2); low ophthalmos and encephalorenal syndrome (OCRL) Inositol polyphosphate-5-phosphatase; pterin-4 alpha-carbinolamine dehydratase 1 (PCBD1); phosphate-modulated endopeptidase X-conjugated (PHEX); sodium channel epithelium 1 subunit alpha (SCNN1A); sodium channel epithelium 1 subunit beta (SCNN1B); sodium channel epithelium 1 subunit gamma (SCNN1G); solute carrier family 12 member 1 (SLC12A1); solute carrier family 12 member 3 (SLC12A3); solute carrier family 1 member 1 (SLC1A1); solute carrier family 2 member 2 (SLC2A2); solute carrier family 34 member 1 (SLC34A1); solute carrier family 34 member 3 (SLC34A3); solute carrier The method according to claim 43, selected from the group consisting of: Rear family 36 member 2 (SLC36A2); solute carrier family 3 member 1 (SLC3A1); solute carrier family 4 member 1 (SLC4A1); solute carrier family 6 member 19 (SLC6A19); solute carrier family 6 member 20 (SLC6A20); solute carrier family 7 member 7 (SLC7A7); solute carrier family 7 member 9 (SLC7A9); transient receptor potential cation channel subfamily M member 6 (TRPM6); WD repeat domain 72 (WDR72); lysine-free (WNK, lysine-deficient) protein kinase 1 (WNK1); lysine-free (WNK, lysine-deficient) protein kinase 4 (WNK4); and combinations thereof. [Claim 46] The method according to claim 43, wherein the introduced gene comprises an inhibitor of a gene or protein selected from the group consisting of renin (REN), sodium channel epithelium subunit 1 alpha (SCNN1A), sodium channel epithelium subunit 1 beta (SCNN1B), and uromodulin (UMOD). [Claim 47] The method according to claim 1, wherein the target circulating serum does not neutralize rAAV upon administration. [Claim 48] The method according to claim 1, wherein the subject has an antibody that neutralizes administered rAAV in the circulating serum, and the antibody does not neutralize rAAV in the kidney at the time of administration. [Claim 49] The method according to claim 1, wherein the subsequent administration of rAAV according to claim 1 is carried out without causing a substantial inflammatory response in the kidney. [Claim 50] The method according to claim 49, wherein the subsequent administration is at least one day later. [Claim 51] The method according to claim 49, wherein the subsequent administration is at least one month later. [Claim 52] The method according to claim 1, wherein the proximal tubules of the kidney are transduced using rAAV. [Claim 53] The method according to claim 1, comprising transducing rAAV into at least one cell population of the glomerulus, glomerular capsule, proximal convoluted tubule, loop of Henle, distal convoluted tubule, or collecting duct of the kidney. [Claim 54] The method according to claim 1, wherein the rAAV includes a kidney-specific promoter. [Claim 55] The method according to claim 54, wherein the kidney-specific promoter is selected from the group consisting of the kidney-specific cadherin (KSPC) gene promoter; the Na+ / glucose cotransporter (SGLT2) gene promoter; the sodium-potassium dichloride cotransporter (NKCC2) gene promoter; and the E-cadherin (ECAD) gene promoter. [Claim 56] The method according to claim 54, wherein the kidney-specific promoter is a synthetic promoter. [Claim 57] The method according to claim 1, wherein the rAAV has a genome comprising a promoter specific to the proximal convoluted tubule and / or collecting duct. [Claim 58] A method for treating renal-related disorders in subjects requiring treatment for renal-related disorders, comprising administering recombinant adeno-associated virus (rAAV) to a subject by carrying out the method according to claim 1. [Claim 59] The method according to claim 58, wherein the kidney-related disorder is selected from the group consisting of autosomal dominant polycystic kidney disease (ADPKD); Alport syndrome; autosomal dominant tubulointerstitial kidney disease (ADTKD); medullary cystic kidney disease; nephronophthria; Bartter syndrome; von Hippel-Lindau syndrome; Gittellmann syndrome; congenital nephrotic syndrome; primary hyperoxaluria; Dent's disease; thin basement nephropathy; cystinuria; Riddle syndrome; papillorenale syndrome; and cystinosis. [Claim 60] Renal-related disorders include apparent mineralocorticoid excess, autosomal dominant hypocalcemia, autosomal dominant hypomagnesemia, Bartter syndrome type 1, Bartter syndrome type 2, Bartter syndrome type 3, Bartter syndrome type 4a, Bartter syndrome type 4b, Bartter syndrome type 5, congenital adrenal hyperplasia type 1, congenital adrenal hyperplasia type 2, congenital adrenal hyperplasia type 4, congenital adrenal hyperplasia type 5, cystinuria type A, cystinuria type B, Dent's disease type 1, Dent's disease type 2 / Lowe syndrome, and dicardia. Silaminoaciduria, distal RTA, EAST / SeSAME syndrome, Fanconi-Bickel syndrome, Fanconi tubular syndrome 1, Fanconi tubular syndrome 2, Fanconi tubular syndrome 3, Fanconi tubular syndrome 4, Gittelmann syndrome, glucocorticoid-treated aldosteronism, HeartNap disorder, hereditary hypophosphatemic rickets with hypercalciuria, HNF1B-related kidney disease, hyperphenylalaninemia BH4 deficiency, hypomagnesemia type 1 / Hypomagnesemia with secondary hypocalcemia, hypomagnesemia type 2, hypomagnesemia type 3 / Familial hypomagnesemia with hypercalciuria and nephrocalcinosis, hypomagnesemia type 4, hypomagnesemia type 5 / Familial hypomagnesemia with hypercalciuria and nephrocalcinosis, hypomagnesemia, seizures, and intellectual disability type 1, hypomagnesemia, seizures, and intellectual disability type 2, iminoglycinuria, Kenny Caffey The method according to claim 58, selected from the group consisting of ey) syndrome type 2, Liddle syndrome, lysinuric protein intolerance, neonatal inflammatory skin and intestinal disease type 2, nephrogenic diabetes insipidus, renal syndrome of inappropriate antidiureticity, pseudohypoaldosteronism type 1, pseudohypoaldosteronism type 1A, pseudohypoaldosteronism type 2b, pseudohypoaldosteronism type 2c, pseudohypoaldosteronism type 2d, pseudohypoaldosteronism type 2e, renal tubular acidosis type 3, and X-linked hypophosphatemic rickets. [Claim 61] The method according to claim 58, wherein the kidney-related disorder is cystinuria and the transgene is SLC3A1 and / or SLC7A9. [Claim 62] The method according to claim 58, wherein the kidney-related disorder is autosomal dominant polycystic kidney disease (ADPKD), and the transgenes are PKD1, PKD2, and / or GANAB. [Claim 63] A method for transducing recombinant adeno-associated virus (rAAV) into at least about 10% of the nephrons in a target kidney, a) Blocking the renal blood vessels of the kidney, selected from the group consisting of the renal artery, renal vein, and combinations thereof; b) Guiding the catheter through the target urethra, bladder, and ureter; c) Administering a solution containing rAAV to the renal pelvis of the kidney via a catheter in a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the body weight of the subject); and d) After administering the solution containing rAAV, release the renal vascular occlusion after a period of approximately 10 to 60 minutes. Includes, Herein lies a method for inducing transduction of at least approximately 10% of nephrons in the kidney by rAAV. [Claim 64] A method for transducing recombinant adeno-associated virus (rAAV) into at least approximately 25% of the nephrons in a target kidney, a) Blocking the renal blood vessels of the kidney, selected from the group consisting of the renal artery, renal vein, and combinations thereof; b) Guiding the catheter through the target urethra, bladder, and ureter; c) Administering a solution containing rAAV to the renal pelvis of the kidney via a catheter in a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the body weight of the subject); and d) After administering the solution containing rAAV, release the renal vascular occlusion after a period of approximately 10 to 60 minutes. Includes, Herein lies a method that results in transduction of at least approximately 25% of nephrons in the kidney by rAAV. [Claim 65] A method for transducing recombinant adeno-associated virus (rAAV) into at least approximately 25% of the nephrons in a target kidney, a) Blocking the renal artery of the kidney, but not blocking the renal vein of the kidney; b) Guiding the catheter through the target urethra, bladder, and ureter; c) Administering a certain volume of a solution containing rAAV into the renal pelvis of the kidney via a catheter; and d) After administering the solution containing rAAV, release the renal artery occlusion approximately 10 to 60 minutes later. Includes, Herein lies a method that results in transduction of at least approximately 25% of nephrons in the kidney by rAAV. [Claim 66] A method for transducing nephrons in the target kidney, a) Blocking renal vessels selected from the group consisting of the renal artery, renal vein, and combinations thereof of the kidney; b) Guiding the catheter through the target urethra, bladder, and ureter; c) Administering a certain volume of a solution containing rAAV other than rAAV9 into the renal pelvis of the kidney via a catheter; and d) After administering the solution containing rAAV, release the renal vascular occlusion after a period of approximately 10 to 60 minutes. Includes, Herein, a method that yields at least twice the transduction efficiency compared to the corresponding transduction efficiency achieved by administering rAAV containing AAV9 capsid to another kidney by the same method. [Claim 67] The method according to claim 66, wherein the rAAV comprises a capsid protein selected from Table 1. [Claim 68] The method according to claim 66, wherein the rAAV has at least twice as high a transduction efficiency in the kidney compared to the corresponding transduction efficiency achieved by administering an rAAV containing an AAV9 capsid to another kidney in the same manner. [Claim 69] The method according to claim 66, wherein the rAAV has a 400-fold higher transduction efficiency in the kidney compared to the corresponding transduction efficiency achieved by administering the rAAV containing AAV9 capsid to another kidney in the same manner. [Claim 70] A method for transducing recombinant adeno-associated virus (rAAV) into at least approximately 25% of the nephrons in a target kidney, a) Isolate the kidney from the systemic circulation; b) Guiding the catheter through the target urethra, bladder, and ureter; c) Administering a solution containing rAAV to the renal pelvis of the kidney via a catheter in a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the body weight of the subject); and d) Re-establish the kidneys into systemic circulation approximately 10 to 60 minutes after administering the solution containing rAAV. Includes, Herein lies a method that results in transduction of at least approximately 25% of nephrons in the kidney by rAAV. [Claim 71] A method for treating kidney damage in a person who requires treatment for kidney damage, Administering a first recombinant adeno-associated virus (rAAV) encoding a transgene that is therapeutic for renal impairment to the target kidney; and The procedure involves administering a first rAAV followed by administering a second rAAV encoding a therapeutic transgene or a different transgene to the target kidney or a different kidney. Includes, Here, the first rAAV and the second rAAV are cross-serologically reactive, and The subject here is a method that does not induce a significant immune response to a second rAAV in the kidney. [Claim 72] At least one solution containing the first and / or second rAAV is at about 25 cmH ２ O ~ approx. 55cmH ２ The method according to claim 71, wherein the drug is administered to the kidney at an intrarenal pressure of O. [Claim 73] The method according to claim 71, wherein a solution containing a second rAAV is administered about one week later. [Claim 74] The first rAAV and / or the second rAAV are To guide a catheter through the target urethra, bladder, and ureter; and Administer a solution containing the first or second rAAV to the renal pelvis of the kidney via a catheter at a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the subject's body weight). The method according to claim 71, wherein the administration is performed by an administration method including the method described above. [Claim 75] The first rAAV and / or the second rAAV are a) Blocking the renal blood vessels of the kidney, selected from the group consisting of the renal artery, renal vein, and combinations thereof; b) Guiding the catheter through the target urethra, bladder, and ureter; c) Administering a certain volume of a solution containing the first or second rAAV to the renal pelvis of a kidney or a different kidney via a catheter at a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the subject's body weight); and d) Reversing renal vascular occlusion approximately 10 to 60 minutes after administering the solution containing the first or second rAAV. The method according to claim 71, wherein the administration is performed by an administration method including the method described above. [Claim 76] The method according to claim 71, which results in at least about 25% of nephrons in the kidney being transduced by rAAV. [Claim 77] The method according to claim 71, wherein the subject has a neutralizing antibody against a first rAAV therapeutic agent prior to administration. [Claim 78] The method according to claim 71, wherein the capsid protein of the first rAAV is of the same serotype as the capsid protein of the second rAAV. [Claim 79] The method according to claim 71, wherein the capsid protein of the first rAAV is of a different serotype from the capsid protein of the second rAAV. [Claim 80] The method according to claim 71, wherein the period for subsequent administration of a second rAAV is determined based on the effectiveness or lifespan of the administration of the first rAAV. [Claim 81] The method according to claim 71, wherein a first rAAV is administered to a target first kidney and a second rAAV is administered to a target second kidney. [Claim 82] The method according to claim 71, wherein a first rAAV is administered to a target first kidney, and a second rAAV is administered to a target first kidney. [Claim 83] The method according to claim 71, wherein a first rAAV is administered to both kidneys of the subject, and a second rAAV is administered to both kidneys of the subject. [Claim 84] A method for treating renal impairment in a patient requiring treatment for renal impairment, wherein the patient is seropositive for recombinant adeno-associated virus (rAAV) therapeutic agents, The target kidney is administered a drug containing an rAAV treatment that encodes a transgene that is therapeutic for kidney damage. Includes, The subject here is a method that does not induce a significant immune response to rAAV treatment agents in the kidney. [Claim 85] The method according to claim 84, wherein the subject has neutralizing antibodies against the rAAV therapeutic agent prior to administration. [Claim 86] rAAV, To guide a catheter through the target urethra, bladder, and ureter; and Administer a solution containing the first or second rAAV to the renal pelvis of the kidney via a catheter at a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the subject's body weight). The method according to claim 84, wherein the administration is performed by an administration method comprising the method described above. [Claim 87] rAAV, a) Blocking the renal blood vessels of the kidney, selected from the group consisting of the renal artery, renal vein, and combinations thereof; b) Guiding the catheter through the target urethra, bladder, and ureter; c) Administering a solution containing rAAV into the renal pelvis of the kidney in a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the body weight of the subject); and d) After administering the solution containing rAAV, relieve the occlusion of the renal blood vessels approximately 10 to 60 minutes later. It is administered by a method of administration that includes, The method according to claim 84, wherein at least about 25% of nephrons in the kidney are transduced by rAAV. [Claim 88] A method for transducing recombinant adeno-associated virus (rAAV) into at least approximately 25% of the nephrons in a target kidney, a) Blocking renal vessels selected from the group consisting of the renal artery, renal vein, and combinations thereof of the kidney; b) Guiding the catheter through the target urethra, bladder, and ureter; c) Administering a solution containing rAAV into the renal pelvis of the kidney via a catheter in a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the body weight of the subject) (where rAAV contains a capsid protein selected from Table 1); and d) After administering the solution containing rAAV, release the renal vascular occlusion after a period of approximately 10 to 60 minutes. Includes, Herein lies a method that results in transduction of at least approximately 25% of nephrons in the kidney by rAAV. [Claim 89] A method for treating kidney-related disorders in subjects requiring treatment of kidney-related disorders, comprising administering rAAV to a subject by carrying out the method according to claim 88. [Claim 90] rAAV is approximately 25 cmH ２ O ~ approx. 55cmH ２ The method according to claim 89, wherein the drug is administered to the kidney at an intrarenal pressure of O. [Claim 91] The method according to claim 89, wherein the volume of the solution is 0.27 mL / kg to 0.33 mL / kg. [Claim 92] The method according to claim 89, wherein the period is 30 to 60 minutes after administration of the solution containing rAAV. [Claim 93] The method according to claim 89, wherein the subject is serologically positive for rAAV before administration of the solution containing rAAV. [Claim 94] The method according to any one of claims 1, 58, 63-66, 70, 71, 84, 88, or 89, wherein rAAV is administered in liposomes, nanocapsules, microparticles, microspheres, lipid particles, lipid nanoparticles, or vesicles. [Claim 95] The method according to any one of claims 1, 58, 63-66, 70, 71, 84, 88, or 89, wherein rAAV is administered to a target using lipid nanoparticles (LNPs). [Claim 96] A pharmaceutical composition containing recombinant adeno-associated virus (rAAV), a) AAV capsid protein selected from Table 1; b) i) Alanine-glyoxylate aminotransferase (AGXT); Bartter syndrome of infants with sensorineural hearing loss (BSND); Chloride voltage-gated channel 5 (CLCN5); Chloride voltage-gated channel Ka (CLCNKA); Chloride voltage-gated channel Kb (CLCNKB); Collagen type IV α3 chain (COL4A3); Collagen type IV α4 chain (COL4A4); Collagen type IV α5 chain (COL4A5); Glucosidase II α subunit (GANAB); Glyoxylate and hydroxypyruvate reductase (GRHPR); Hepatocyte nuclear factor 1 (HNF1) homeobox B (HNF1B); 4-hydroxy-2-oxoglutarate aldolase 1 (HOGA1); Potassium inward rectifier channel subfamily J member 1 (KCNJ1); MAGED2 ( Genes selected from the group consisting of: type V); mucin 1 (MUC1); nephrocystin 1 (NPHP1); nephrin (NPHS1); nephrotic syndrome 2 (NPHS2; podosin); inositol polyphosphate-5-phosphatase (OCRL); polycystin 1 (PKD1); polycystin 2 (PKD2); polycystin 1 (PKHD1); protein transport protein Sec61 subunit α isoform 1 (SEC61A1); solute carrier family 12 member 1 (SLC12A1); solute carrier family 12 member 3 (SLC12A3); solute carrier family 3 member 1 (SLC3A1); solute carrier family 7 member 9 (SLC7A9); von Hippel-Lindau tumor suppressor (VHL); and combinations thereof; or ii) Inhibitors of genes or proteins selected from the group consisting of renin (REN), sodium channel epithelium subunit 1 alpha (SCNN1A), sodium channel epithelium subunit 1 beta (SCNN1B), and uromodulin (UMOD). Transgenes containing; and c) Pharmaceutically acceptable carriers A pharmaceutical composition containing the above. [Claim 97] A pharmaceutical composition containing recombinant adeno-associated virus (rAAV), a) AAV capsid protein selected from Table 1; b) Aquaporin 2 (AQP2); ATPase Na+ / K+ transport subunit alpha-1 (ATP1A1); ATPase H+ transport V0 subunit A4 (ATP6V0A4); ATPase H+ transport V1 subunit B1 (ATP6V1B1); arginine vasopressin receptor 2 (AVPR2); vertine CLCNK (chloride channel K) type accessory subunit beta (BSND); carbonic anhydrase 2 (CA2); calcium-sensing receptor (CaSR); chloride voltage-gated channel 5 (CLCN5); CLCNKA (chloride voltage-gated channel Ka); Chloride voltage-gated channel Kb (CLCNKB); Claudin 16 (CLDN16); Claudin 19 (CLDN19); Cyclin and CBS domain divalent metal cation transport mediator 2 (CNNM2); Karin 3 (CUL3); Cytochrome P450 family 11 subfamily B member 1 (CYP11B1); Cytochrome P450 family 11 subfamily B member 2 (CYP11B2); Cytochrome P450 family 17 subfamily A member 1 (CYP17A1); Cytochrome P450 family 21 Subfamily A member 2 (CYP21A2); epidermal growth factor (EGF); epidermal growth factor receptor (EGFR); enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase (EHHADH); FAM111 (Family 111) trypsin-like peptidase A (FAM111A); forkhead box I1 (FOXI1); FXYD domain / motif-containing ion transport regulator 2 (FXYD2); glycine amidinotransferase (GATM); guanine nucleotide-binding protein; alpha-stimulator (GNAS); Hepatocyte nuclear factor 1 (HNF1) homeobox B (HNF1B); hepatocyte nuclear factor 4 alpha (HNF4A); hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2); hydroxy-delta-5-steroid dehydrogenase, 3-beta- and steroid delta-isomerase 2 (HSD3B2); potassium voltage-gated channel subfamily A member 1 (KCNA1); potassium inward rectifier channel subfamily J member 1 (KCNJ1); potassium inward rectifier channel subfamily J member 10 (KCNJ10);Kelch family member 3 (KLHL3); melanoma antigen gene family member D2 (MAGED2); nuclear receptor subfamily 3 group C member 2 (NR3C2); low ophthalmos and encephalorenal syndrome (OCRL) Inositol polyphosphate-5-phosphatase; pterin-4-alpha-carbinolamine dehydratase 1 (PCBD1); phosphate-modulated endopeptidase X-conjugated (PHEX); sodium channel epithelium subunit 1 alpha (SCNN1A); sodium channel epithelium subunit 1 beta (SCNN1B); sodium channel epithelium subunit 1 gamma (SCNN1G); solute carrier family 12 member 1 (SLC12A1); solute carrier family 12 member 3 (SLC12A3); solute carrier family 1 member 1 (SLC1A1); solute carrier family 2 member 2 (SLC2A2); solute carrier family 34 member 1 (SLC34A1); solute carrier family 34 member 3 (SLC34A3); solute carrier Transgenes comprising genes selected from the group consisting of Family 36 Member 2 (SLC36A2); Solute Carrier Family 3 Member 1 (SLC3A1); Solute Carrier Family 4 Member 1 (SLC4A1); Solute Carrier Family 6 Member 19 (SLC6A19); Solute Carrier Family 6 Member 20 (SLC6A20); Solute Carrier Family 7 Member 7 (SLC7A7); Solute Carrier Family 7 Member 9 (SLC7A9); Transient Receptor Potential Cation Channel Subfamily M Member 6 (TRPM6); WD Repeat Domain 72 (WDR72); Lysine-Free (WNK, Lysine-Deficient) Protein Kinase 1 (WNK1); Lysine-Free (WNK, Lysine-Deficient) Protein Kinase 4 (WNK4); and combinations thereof; and; c) Pharmaceutically acceptable carriers A pharmaceutical composition containing the following: [Claim 98] The pharmaceutical composition according to claim 96 or 97, wherein the pharmaceutically acceptable carrier comprises mannitol. [Claim 99] The pharmaceutical composition according to claim 96 or 97, wherein AAV comprises the AAV2G9 capsid protein. [Claim 100] A solution containing rAAV, ８ Viral genome / mL (vg / mL) ~ 10 １５ The pharmaceutical composition according to claim 96 or 97, having a concentration of vg / mL. [Claim 101] A solution containing rAAV, ８ vg / mL ~ 10 １３ The pharmaceutical composition according to claim 96 or 97, having a concentration of vg / mL. [Claim 102] Total 1 x 10 １３ ~2 x 10 １３ A pharmaceutical composition according to claim 96 or 97, comprising the rAAV virus genome. [Claim 103] Total 5 x 10 １３ ~6 x 10 １３ A pharmaceutical composition according to claim 96 or 97, comprising the rAAV virus genome. [Claim 104] The pharmaceutical composition according to claim 96 or 97, having a unit dose of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the body weight of the subject). [Claim 105] The pharmaceutical composition according to claim 96 or 97, wherein the unit dose is approximately 0.27 mL / kg to approximately 0.33 mL / kg. [Claim 106] The pharmaceutical composition according to claim 96 or 97, wherein the introduced gene contains a reporter protein. [Claim 107] The pharmaceutical composition according to claim 96 or 97, wherein the rAAV genome contains a kidney-specific promoter. [Claim 108] The pharmaceutical composition according to claim 107, wherein the kidney-specific promoter is selected from the group consisting of the kidney-specific cadherin (KSPC) gene promoter; the Na+ / glucose cotransporter (SGLT2) gene promoter; the sodium potassium dichloride cotransporter (NKCC2) gene promoter; and the E-cadherin (ECAD) gene promoter. [Claim 109] The pharmaceutical composition according to claim 107, wherein the kidney-specific promoter is a synthetic promoter. [Claim 110] The pharmaceutical composition according to claim 96 or 97, wherein the rAAV genome comprises a promoter specific to the proximal convoluted tubule and / or collecting duct. [Claim 111] The pharmaceutical composition according to claim 96 or 97, wherein rAAV is formulated in liposomes, nanocapsules, microparticles, microspheres, lipid particles, lipid nanoparticles, or vesicles for delivery. [Claim 112] The pharmaceutical composition according to claim 96 or 97, wherein rAAV is formulated for delivery by lipid nanoparticles (LNPs). [Claim 113] A method for transducing recombinant adeno-associated virus (rAAV) into nephrons in a target kidney, comprising: guiding a catheter through the urethra, bladder, and ureter of the target; and administering a solution containing rAAV to the renal pelvis of the kidney in a volume of approximately 0.13 mL / kg to approximately 0.33 mL / kg (where kg is the body weight of the target), wherein the rAAV contains AAV2G9, and the renal nephrons are transduced with high efficiency by rAAV.

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